1,015 results on '"Ethionine pharmacology"'
Search Results
152. Reversal of ethionine-induced growth inhibition of Escherichia coli by adenosine triphosphate.
- Author
-
Norris WE Jr and Winston AJ
- Subjects
- Escherichia coli growth & development, Methionine pharmacology, Adenosine Triphosphate pharmacology, Escherichia coli drug effects, Ethionine pharmacology
- Published
- 1973
- Full Text
- View/download PDF
153. [Effect of vitamin E on adenine and flavin nucleotides in the rat liver after the administration of ethionine].
- Author
-
Kuznetsova LN, Simonova NIa, and Shtutman TsM
- Subjects
- Adenosine Diphosphate metabolism, Adenosine Monophosphate metabolism, Adenosine Triphosphate metabolism, Animals, Electrophoresis, Paper, Liver cytology, Liver metabolism, Male, Methionine pharmacology, Rats, Spectrometry, Fluorescence, Subcellular Fractions analysis, Adenine Nucleotides metabolism, Ethionine pharmacology, Flavin Mononucleotide metabolism, Flavin-Adenine Dinucleotide metabolism, Liver drug effects, Vitamin E pharmacology
- Published
- 1974
154. The effects of S-adenosyl methionine (AdoMet) and its analogues on the control of transcription and translation in vitro of the mRNA products of two cytoplasmic polyhedrosis viruses.
- Author
-
Mertens PP and Payne CC
- Subjects
- Adenosine pharmacology, Cell-Free System, Ethionine pharmacology, Insect Viruses drug effects, Insect Viruses enzymology, Kinetics, Plants metabolism, Ribonucleotides pharmacology, Species Specificity, Triticum metabolism, Adenosine analogs & derivatives, DNA-Directed RNA Polymerases metabolism, Ethionine analogs & derivatives, Homocysteine analogs & derivatives, Insect Viruses genetics, Protein Biosynthesis drug effects, RNA, Messenger genetics, S-Adenosylhomocysteine pharmacology, S-Adenosylmethionine pharmacology, Transcription, Genetic drug effects
- Abstract
S-Adenosyl methionine (AdoMet) and several structurally related compounds were added to in vitro systems for the synthesis of single-stranded RNA by cytoplasmic polyhedrosis virus (CPV) types 1 and 2. The effects of these compounds were examined on the level of transcription and methylation of the RNA products. Of the compounds tested, five increased the polymerase activity in both viruses, the most effective being the D- and L-stereoisomers of S-adenosyl homocysteine (AdoHcy), and the least effective, adenosine. L-AdoHcy, unlike D-AdoHcy, was also a competitive inhibitor of RNA methylation in the presence of [3H]AdoMet. The different response of both viruses to D- and L-AdoHcy suggests that CPV virions contain at least two functionally distinct sites to which AdoMet, or its analogues, bind. One of these is the transcription control site, while the other is the active site(s) for RNA methylation. CPV RNA synthesised in the presence of the methyl donor AdoMet was more efficiently translated in vitro in a wheat-germ translation system than RNA synthesised in the presence of methylation inhibitors. Type 2 CPV-RNA transcripts had a greater degree of methylation than type 1 CPV transcripts and were more effective in stimulating protein synthesis in the translation system. It seems likely that the allosteric control of CPV polymerase by AdoMet and its analogues, and the methylation of the transcripts, ensures the effective transcription and translation of the CPV genome and the stability of the viral messenger RNA.
- Published
- 1983
- Full Text
- View/download PDF
155. Effect of carcinogen ethionine on enzymatic methylation of DNA sequences with various degrees of repetitiveness.
- Author
-
Boehm TL and Drahovsky D
- Subjects
- Animals, Base Sequence, Mast-Cell Sarcoma drug therapy, Methylation, Mice, Mice, Inbred Strains, Sarcoma, Experimental metabolism, DNA (Cytosine-5-)-Methyltransferases antagonists & inhibitors, DNA, Neoplasm metabolism, Ethionine pharmacology, Mast-Cell Sarcoma metabolism, Methyltransferases antagonists & inhibitors
- Published
- 1979
- Full Text
- View/download PDF
156. On some properties of five mutator alleles in Schizosaccharomyces pombe.
- Author
-
Munz P
- Subjects
- Crosses, Genetic, Diploidy, Drug Resistance, Microbial, Ethionine pharmacology, Genotype, Probability, Alleles, Ascomycota radiation effects, Mutation, Radiation Genetics, Schizosaccharomyces radiation effects, Ultraviolet Rays
- Published
- 1975
- Full Text
- View/download PDF
157. Poly(adenosine diphosphoribose) polymerase activity and adenosine diphosphate ribosylation of proteins during pancreatic degeneration and regeneration.
- Author
-
Savard P, Aubin R, Whish WJ, Lord A, and Poirier GG
- Subjects
- Animals, Autoradiography, Cell Nucleus enzymology, Ethionine pharmacology, Male, Microscopy, Electron, Pancreas drug effects, Pancreas physiology, Rats, Regeneration, Ribose metabolism, Adenosine Diphosphate metabolism, NAD+ Nucleosidase metabolism, Nucleoside Diphosphate Sugars biosynthesis, Pancreas enzymology, Poly Adenosine Diphosphate Ribose biosynthesis, Poly(ADP-ribose) Polymerases metabolism, Protein Biosynthesis, Proteins
- Abstract
The activity of poly(adenosine diphosphoribose) polymerase was measured in isolated rat pancreatic nuclei and was found to increase during pancreatic nuclei which follows an ethionine treatment, although a possible relationship of enzyme activity to the initial degenerative phase may also be considered. There is a 2-fold increase in the enzyme activity during the destruction process which remains high during the regeneration period. This increase of activity observed during regeneration is not related to a decrease of the polymer degradation. We have studied the adenosine diphosphate ribosylation of proteins during pancreatic regeneration, and we have found increases in the level of adenosine diphosphate ribosylations of these proteins just before regeneration and during the regeneration period. The in vivo adenosine diphosphate ribosylation of nuclear proteins does not correlate with synthetase activity measured in nuclei during the degeneration period but does correlate during the regeneration period and thereafter with the relative amount of enzymatic activity found in nuclei. Furthermore, as verified by autoradiography, labeling of the nuclei by polyadenosine diphosphoribose polymer shows a marked increase during regeneration.
- Published
- 1981
158. 5'-Nucleotidase activity in liver homogenates of rats treated with CCl4, colchicine, cycloheximide, emetine, ethanol, ethionine and 5-fluorotryptophan.
- Author
-
Agostini C, Secchi M, and Venturelli D
- Subjects
- Animals, Colchicine pharmacology, Cycloheximide pharmacology, Emetine pharmacology, Ethanol pharmacology, Ethionine pharmacology, Female, Liver drug effects, Male, Rats, Sex Factors, Tryptophan analogs & derivatives, Tryptophan pharmacology, Carbon Tetrachloride Poisoning enzymology, Liver enzymology, Nucleotidases metabolism
- Abstract
5'-Nucleotidase activity an enzyme marker of the plasma membranes, increases in female rat liver homogenates following ethionine administration, while homogenates from males show no changes. Treatment with CCl4, colchicine, cycloheximide, emetine, ethanol and 5-fluorotryptophan does not significantly modify the 5'-nucleotidase activity of liver homogenates of either female or male rats.
- Published
- 1980
- Full Text
- View/download PDF
159. Effects of ethionine on tRNA methylation in male and female rats.
- Author
-
Wainfan E and Balis ME
- Subjects
- Animals, Female, Liver drug effects, Male, Rats, Sex Factors, Ethionine pharmacology, Liver metabolism, RNA, Transfer metabolism, tRNA Methyltransferases metabolism
- Published
- 1979
- Full Text
- View/download PDF
160. Selective inhibition of uracil tRNA methylases of E. coli by ethionine.
- Author
-
Tscherne JS and Wainfan E
- Subjects
- Amino Acids pharmacology, Escherichia coli enzymology, Ethionine analogs & derivatives, Molecular Conformation, S-Adenosylmethionine pharmacology, Structure-Activity Relationship, Substrate Specificity, Uracil, Ethionine pharmacology, tRNA Methyltransferases antagonists & inhibitors
- Abstract
L-ethionine has been found to inhibit uracil tRNA methylating enzymes in vitro under conditions where methylation of other tRNA bases is unaffected. No selective inhibitor for uracil tRNA methylases has been identified previously. 15 mM L-ethionine or 30 mM D,L-ethionine caused about 40% inhibition of tRNA methylation catalyzed by enzyme extracts from E. coli B or E. coli M3S (mixtures of methylases for uracil, guanine, cytosine, and adenine) but did not inhibit the activity of preparations from an E. coli mutant that lacks uracil tRNA methylase. Analysis of the 14CH3 bases in methyl-deficient E. coli tRNA after its in vitro methylation with E. coli B3 enzymes in the presence or absence of ethionine showed that ethionine inhibited 14CH3 transfer to uracil in tRNA, but did not diminish significantly the 14CH3 transfer to other tRNA bases. Under similar conditions 0.6 mM S-adenosylethionine and 0.2 mM ethylthioadenosine inhibited the overall tRNA base methylating activity of E. coli B preparations about 50% but neither of these ethionine metabolites preferentially inhibited uracil methylation. Ethionine was not competitive with S-adenosyl methionine. Uracil methylation was not inhibited by alanine, valine, or ethionine sulfoxide. It is suggested that the thymine deficiency that we found earlier in tRNA from ethionine-treated E. coli B cells, resulted from base specific inhibition by the amino acid, ethionine, of uracil tRNA methylation in vivo.
- Published
- 1978
- Full Text
- View/download PDF
161. Increased activity of rat liver N2-guanine tRNA methyltransferase II in response to liver damage.
- Author
-
Wainfan E, Dizik M, and Balis ME
- Subjects
- 2-Acetylaminofluorene pharmacology, Animals, Carbon Tetrachloride Poisoning enzymology, Escherichia coli, Ethionine pharmacology, Female, Hepatectomy, Hot Temperature, Liver drug effects, Male, Phenobarbital pharmacology, RNA, Transfer, Amino Acyl metabolism, Rats, Rats, Inbred Strains, Liver enzymology, RNA, Transfer, Met, tRNA Methyltransferases metabolism
- Abstract
Alterations in rat liver transfer RNA (tRNA) methyltransferase activities have been observed after liver damage by various chemicals or by partial hepatectomy. The qualitative and quantitative nature of these activity changes and the time course for their induction have been studied. Since homologous tRNAs are essentially fully modified in vivo, E. coli tRNAs were used as in vitro substrates for the rat liver enzymes in these studies. Each of the liver-damaging agents tested rapidly caused increases in activities of the enzyme(s) catalyzing methyl group transfer to tRNAs that have an unmodified guanine at position 26 from the 5' end of the molecule. This group of tRNAs includes E. coli tRNANfmet, tRNAAla1, tRNALeu1, or Leu2, and tRNASer3 (Group 1). In each case N2-methylguanine and N2,N2-dimethylguanine represented 90% or more of the products of these in vitro methylations. The product and substrate specificity observed are characteristic of N2-guanine methyltransferase II (S-adenosyl-L-methionine : tRNA (guanine-2)-methyltransferase, EC 2.1.1.32). In crude and partially purified preparations derived from livers of both control and treated animals this enzyme activity was not diminished significantly by exposure to 50 degrees C for min. The same liver-damaging agents induced little or no change in the activities of enzymes that catalyze methyl group transfer to various other E. coli tRNAs that do not have guanine at position 26 (Group 2). The results of mixing experiments appear to rule out the likelihood that the observed enzyme activity changes are due to stimulatory or inhibitory materials present in the enzyme preparations from control or treated animals. Thus, our experiments indicate that liver damage by each of several different methods, including surgery or administration of chemicals that are strong carcinogens, hepatotoxins, or cancer-promoting substances, all produce changes in liver tRNA methyltransferase activity that represent a selective increase in activity of N2-guanine tRNA methyltransferase II. It is proposed that the specificity of this change is not fortuitous, but is the manifestation of an as yet unidentified regulatory process.
- Published
- 1984
- Full Text
- View/download PDF
162. The effect of ionophore A23187 and 2,4-dinitrophenol on the structure and function of cultured liver cells.
- Author
-
George M, Chenery RJ, and Krishna G
- Subjects
- 2,4-Dinitrophenol, Adenosine Triphosphate metabolism, Animals, Cells, Cultured, Chemical and Drug Induced Liver Injury physiopathology, Ethionine pharmacology, L-Lactate Dehydrogenase metabolism, Liver cytology, Male, Microscopy, Electron, Scanning, Rats, Rats, Inbred Strains, Anti-Bacterial Agents pharmacology, Calcimycin pharmacology, Dinitrophenols pharmacology, Liver drug effects
- Published
- 1982
- Full Text
- View/download PDF
163. [Is hypomethylation of cellular DNA a step required in the initiation process of chemical carcinogenesis?].
- Author
-
Shi ZZ, Yu YN, and Chen XR
- Subjects
- Aflatoxin B1, Aflatoxins pharmacology, Azacitidine pharmacology, Cells, Cultured, DNA metabolism, Epithelial Cells, Ethionine pharmacology, Humans, Methylation, Methylnitronitrosoguanidine pharmacology, Amnion cytology, Carcinogens pharmacology, DNA drug effects
- Abstract
There seems to be a current view that the inhibition of DNA methylation may be a mechanism of initiation of carcinogenesis or one of the steps required in the carcinogenic process. However, because of the deficiencies in research works on cellular level, there is a long way to make such a general relationship between carcinogen and the inhibition of cellular DNA methylation. In this paper the effects of some chemical carcinogens on methylation of newly replicated DNA in human FL cells was analyzed by comparing the weight average length (Lw) of the DNA digests after complete digestion by restriction endonuclease Hpa II. It was observed that two non-genotoxic carcinogens (5-azacytidine and L-ethionine) and two genotoxic carcinogens (MNNG and aflatoxin B1) used in this study all caused obvious cytotoxicity on FL cells at the test concentration. Five days after the termination of 5-azacytidine treatment (2 x 10(-6) M, 24 hours), Lw (kb) of the Hpa II digests of cellular DNA was smaller than that of control (8.0 +/- 0.1 vs 10.9 +/- 1.0, P less than 0.01), the Lw change rate was -27%. When DNA was analyzed from FL cells after 9 days continuous treatment of L-ethionine (2 x 10 M), the digestibility of Hpa II was also increased as compared with that of the control, the Lw values (kb) showed a decrease of about 8% (9.8 +/- 0.3 vs 10.6 +/- 0.3, P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
- Published
- 1989
164. A rapid liquid chromatographic determination of S-adenosylhomocysteine in subgram amounts of tissue.
- Author
-
Hoffman J
- Subjects
- Animals, Chromatography, High Pressure Liquid methods, Ethionine pharmacology, Female, Liver analysis, Liver drug effects, Liver metabolism, Mice, Mice, Inbred C57BL, Microchemistry, Rats, Homocysteine analogs & derivatives, S-Adenosylhomocysteine analysis, S-Adenosylhomocysteine metabolism, S-Adenosylmethionine analysis, S-Adenosylmethionine metabolism
- Published
- 1975
- Full Text
- View/download PDF
165. Plasma and tissue iron changes in the rat after acute administration of ethionine.
- Author
-
Loh TT and Archdeacon JW
- Subjects
- Animals, Erythrocytes drug effects, Erythrocytes metabolism, Ethionine antagonists & inhibitors, Female, Iron blood, Liver drug effects, Liver metabolism, Osmotic Fragility drug effects, Rats, Spleen drug effects, Spleen metabolism, Time Factors, Transferrin metabolism, Ethionine pharmacology, Iron metabolism
- Abstract
1. Ethionine administered acutely to the adult female rat markedly elevates and then lowers plasma iron concentration over several days. Liver iron undergoes a reverse cycle. 2. Ethionine does not cause changes in the blood parameters, including total plasma iron-binding capacity and plasma iron clearance. Erythrocytes of rats injected with ethionine show altered responses to hypertonicity. 3. Increased reticulo-endothelial activity of the spleen, indicated by increased uptake of 59Fe-labelled erythrocytes by liver and spleen, apparently contributes to plasma iron elevation. Also the liver releases iron which further raises plasma iron.
- Published
- 1975
- Full Text
- View/download PDF
166. Chemical carcinogenesis. I. Rat liver tRNA ethylation by ethionine.
- Author
-
Kanduc D
- Subjects
- Animals, Chemical Phenomena, Chemistry, Guanosine metabolism, Rats, Ethionine pharmacology, Liver metabolism, RNA, Transfer metabolism
- Abstract
The mechanism of biological action of the powerful carcinogen ethionine is still unknown at the present. Here the "in vivo" tRNA ethylation after administration of radioactive ethionine to rats has been reinvestigated. In particular, the radioactive "pyrimidine nucleotides" fraction was examined: chromatographic and ultraviolet-spectral analyses indicated the presence of imidazole-ring-opened derivatives of guanosine in this fraction, the identification of which is reported in the accompanying paper. These data appear particularly interesting especially when considering the recently advanced hypothesis (6,7) of a transversion purine----pyrimidine as the initial precancerous biochemical lesion in chemical carcinogenesis.
- Published
- 1984
167. Anaplastic carcinomas in nude mice and in original donor strain rats inoculated with cultured oval cells.
- Author
-
Yoshimura H, Harris R, Yokoyama S, Takahashi S, Sells MA, Pan SF, and Lombardi B
- Subjects
- Animals, Carcinoma pathology, Carcinoma ultrastructure, Cells, Cultured, Ethionine pharmacology, Liver cytology, Liver Neoplasms pathology, Liver Neoplasms ultrastructure, Mice, Mice, Nude, Rats, Rats, Inbred Strains, Transplantation, Heterologous, Transplantation, Homologous, Cell Transformation, Neoplastic, Epithelial Cells, Erythrocytes, Abnormal transplantation
- Abstract
Male Sprague-Dawley rats were fed for 4-5 weeks a choline-devoid diet containing 0.1% DL-ethionine. Preparations of nonparenchymal epithelial cells, enriched in oval cells, were isolated from the livers of these animals and were placed in culture. Six lines of hepatic epithelial cells were thus established. The lines underwent transformation after several passages, became tumorigenic in nude mice and 3 lines also in rats of the same strain of origin of the isolated cells. The tumors were uniformly highly anaplastic carcinomas. Preliminary morphologic, cytologic, and cytochemical results were consistent with the tumoral cells being hepatocytelike cells. These findings are viewed and discussed in terms of the cellular source, in vivo, of longterm cultures of rat liver epithelial cells, and in relation to a possible role of hepatic nonparenchymal epithelial cells in the process of hepatocellular tumor induction by chemical carcinogens.
- Published
- 1983
168. Separation of two populations of cells with gamma-glutamyl transpeptidase from carcinogen-treated rat liver.
- Author
-
Jacobs JM, Pretlow TP, Fausto N, Pitts AM, and Pretlow TG 2nd
- Subjects
- Animals, Cell Separation methods, Centrifugation, Density Gradient methods, Ethionine pharmacology, Glucose-6-Phosphatase analysis, Histocytochemistry, Iron analysis, Liver drug effects, Liver pathology, Liver Neoplasms chemically induced, Liver Neoplasms diagnosis, Male, Neoplasms, Experimental chemically induced, Neoplasms, Experimental diagnosis, Rats, Clinical Enzyme Tests, Liver enzymology, Precancerous Conditions diagnosis, gamma-Glutamyltransferase analysis
- Abstract
Noninbred Sprague-Dawley rats were maintained on a choline-deficient diet containing 0.05% ethionine. After 10-13 weeks, livers were dispersed with collagenase, lysozyme, collagenase and hyaluronidase. Pronase, or a selected batch of trypsin. The highest yield of cells with histochemically demonstrable gamma-glutamyl transpeptidase (GGT) was obtained with trypsin. After velocity sedimentation in an isokinetic gradient of Ficoll in tissue culture medium, two modal populations of cells with histochemically demonstrable GGT were observed. The first mode contained cells that were morphologically different from hepatocytes and that may be oval cells. The second, more rapidly sedimenting modal population of cells with GGT was morphologically similar to hepatocytes as assessed with Wright's stain; the location of this population in the gradient was the same as the location of cells with the appearance of hepatocytes that lacked iron and that had decreased glucose 6-phosphatase. In multiple experiments, the purest fractions contained 71.7 +/- 3.5% cells (mean +/- SD) with the appearance of hepatocytes with histochemically demonstrable GGT.
- Published
- 1981
169. Effect of reduced hepatic energy state on acetaminophen conjugation in rats.
- Author
-
Dills RL and Klaassen CD
- Subjects
- Acetaminophen analogs & derivatives, Adenine Nucleotides metabolism, Animals, Bile metabolism, Ethionine pharmacology, Fructose pharmacology, Kinetics, Male, Phosphates metabolism, Rats, Rats, Inbred Strains, Uracil Nucleotides metabolism, Uridine Diphosphate Glucose metabolism, Acetaminophen metabolism, Energy Metabolism, Liver metabolism
- Abstract
The effect of decreased hepatic energy state on xenobiotic conjugation was examined in vivo. The pharmacokinetics of acetaminophen, a drug that is conjugated with glucuronic acid, sulfate and glutathione, was analyzed in rats when the hepatic energy state had been decreased by ethionine or fructose. Treatment with ethionine or fructose reduced the hepatic adenosine triphosphate/diphosphate ratio by 30 to 65% and 43 to 54% and the phosphorylation potential by 50 to 80 and 43%, respectively. Ethionine treatment increased uridine triphosphate (UTP) and other UTP-derived nucleotides. However, uridine diphosphoglucuronic acid levels were decreased by 44% whereas uridine diphosphoglucose concentration was increased by 20%. This effect may be due to a decrease in redox state. Fructose treatment reduced the concentrations of UTP and UTP-derived nucleotides. Uridine diphosphoglucose was reduced by 50% and uridine diphosphoglucuronic acid by about 40%. Ethionine and fructose also decreased glutathione and adenosine 3'-phosphate 5'-phosphosulfate concentrations in the liver by 30 to 50%. During the period of decreased energy state, biliary and urinary excretion of acetaminophen (2 mmol/kg i.v.) and its metabolites was reduced 57% by ethionine and 66% by fructose. This was caused by decreased synthesis and excretion of the conjugates. Synthesis of the conjugates was impaired because of decreased hepatic cosubstrate levels. The present data suggest that energy state must be severely compromised before decreases in conjugation are observed in vivo. Thus, it is unlikely that energy state is often a limitation in the conjugation and excretion of xenobiotics.
- Published
- 1986
170. Ethionine-resistant mutants of some Candida strains.
- Author
-
Kvitko KV and Soom YaO
- Subjects
- Candida drug effects, Drug Resistance, Microbial, Ethionine pharmacology, Mutation drug effects
- Published
- 1974
171. The dependence of glucose formation from lactate on the adenosine triphosphate content in the isolated perfused rat liver.
- Author
-
Wilkening J, Nowack J, and Decker K
- Subjects
- Acetoacetates biosynthesis, Adenosine pharmacology, Adenosine Triphosphate pharmacology, Animals, Ethionine pharmacology, Hydroxybutyrates biosynthesis, Kinetics, Liver drug effects, Oxygen Consumption drug effects, Perfusion, Rats, Time Factors, Urea biosynthesis, Adenosine Triphosphate physiology, Gluconeogenesis drug effects, Lactates metabolism, Liver metabolism
- Abstract
Bilateral intercollicular lesions in the chick abolish or depress notonly calling, but also those phases of behavior when calling would have been occurring. These include: long bouts of excited feeding immediately after food is made available;examining and pecking moving targets and novel objects; persistent scanning, and inhibitionof other behaviour in a novel environment. Deaf birds behave precisely like controls,so that possible auditory deficits are not involved. During calling phases significantvisual stimuli are treated as if they were startling or conspicuous. Conversely,continuousexamination of a stimulus causes calling to diminish or disappear even though responsecontinues; a brief period when the stimulus is not seen causes calling to begin againwhen it is once more perceived. In addition to the increased effectiveness of relevantvisual stimuli, motor facilitation is usual in calling phases, as is inhibition ofirrelevant responses. Emotioanl behaviour in man and other mammals is composed tocalling phases in the chick
- Published
- 1975
- Full Text
- View/download PDF
172. Methionine metabolism in BHK cells: selection and characterization of ethionine resistant clones.
- Author
-
Caboche M
- Subjects
- 5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase metabolism, Cell Division drug effects, Cell Line, Drug Resistance, Ethionine metabolism, Folic Acid pharmacology, Homocysteine metabolism, Methionine analogs & derivatives, Methionine pharmacology, Methionine Adenosyltransferase metabolism, Mutation, Norleucine toxicity, Quinone Reductases metabolism, Selenomethionine toxicity, Vitamin K, Clone Cells drug effects, Ethionine pharmacology, Methionine metabolism
- Abstract
The selection of clones resistant to methionine antagonists was undertaken on baby hamster Kidney cells grown in a methionine free medium, supplemented with homocystine, folic acid and hydroxo-B12. Clones resistant to 30 mug/ml ethionine were isolated after mutagenesis at an induced mutation frequency of 2.3 X 10(-5). An ethionine resistant clone, ETH 304, was extensively studied. The resistant cells excreted methionine in the culture medium and the intracellular pools of methionine and SAM were two to five times greater in the resistant clone than in the wild type cells. A semidominant ethionine resistant phenotype was observed in hybrids between the wild type and this resistant clone. Measurement of the specific activity of menadione reductase, B12 methyltransferase and ATP: L-methionine S-adenosyl-transferase in crude extracts of the wild type showed a repressive action of methionine on the level of the three enzymes. However, the ethionine resistant clone ETH 304 was not modified in this function. Menadione reductase is feedback-inhibited by SAM in wild type cells. The enzyme of the ethionine resistant clone was significantly less sensitive to SAM. When a comparison of thermal stability was made between the wild type and ethionine resistant clone enzymes, it was found that the thermal stability of the latter was modified. Three other ethionine resistant clones, independantly isolated, were similarly affected in the properties of menadione reductase. These results suggest that the pathway of re-use of S-adenosyl homocysteine, produced during methylation reactions, is highly regulated by methionine and SAM.
- Published
- 1976
- Full Text
- View/download PDF
173. Synthesis of viral-specific polypeptides in Mengo virus-infected L cells: evidence for asymmetric translation of the viral genome.
- Author
-
Paucha E, Seehafer J, and Colter JS
- Subjects
- Amino Acids metabolism, Animals, Antibiotics, Antineoplastic pharmacology, Canavanine pharmacology, Carbon Radioisotopes, Dactinomycin pharmacology, Electrophoresis, Polyacrylamide Gel, Ethionine pharmacology, Genes, Genetic Variation, L Cells, Mice, Molecular Weight, Peptides metabolism, Phenylalanine analogs & derivatives, Phenylalanine pharmacology, Proline analogs & derivatives, Proline pharmacology, Tritium, Viral Proteins metabolism, Mengovirus metabolism, Peptide Biosynthesis, Protein Biosynthesis drug effects, Viral Proteins biosynthesis
- Published
- 1974
- Full Text
- View/download PDF
174. Properties of ribosomes and RNA synthesized by Escherichia coli grown in the presence of ethionine. 3. Methylated proteins in 50 S ribosomes of E. coli EA2.
- Author
-
Alix JH and Hayes D
- Subjects
- Amino Acids enzymology, Carbon Radioisotopes, Chromatography, Paper, Electrophoresis, Paper, Electrophoresis, Polyacrylamide Gel, Escherichia coli analysis, Escherichia coli enzymology, Magnesium pharmacology, Methylation, Methyltransferases analysis, Ribosomes enzymology, Tritium, Bacterial Proteins analysis, Escherichia coli drug effects, Ethionine pharmacology, RNA, Bacterial analysis, RNA, Ribosomal analysis, Ribosomes analysis
- Published
- 1974
- Full Text
- View/download PDF
175. The persistence of maternal inheritance in Chlamydomonas despite hypomethylation of chloroplast DNA induced by inhibitors.
- Author
-
Feng TY and Chiang KS
- Subjects
- Azacitidine pharmacology, Chloroplasts physiology, Ethionine pharmacology, Extrachromosomal Inheritance, Chlamydomonas genetics, Methylation
- Abstract
We have used inhibitors of methylation to evaluate the proposal that the extent of methylation of chloroplast DNA ( cpDNA ) of the mating type-plus (mt+) parent occurring during gametogenesis in wild-type Chlamydomonas renhardtii is directly correlated with the uniparental transmission of chloroplast genes by this parent [ Sager , R., Grabowy , C. & Sano , H. (1981) Cell 24, 41-47]. As detected by high-pressure liquid chromatography, the methylation of cpDNA was at its lowest level in the vegetative stage; the mt+ cells had a deoxycytidine methylation index (the percentage of deoxycytidine methylated) of 0.5, while the mating type-minus (mt-) index was lower by at least a factor of 3. This basal level of cpDNA methylation increased more than 20-fold after gametogenesis to give a methylation index of 12.1 and 4.3 for mt+ and mt- gametes, respectively. Another striking increase was detected at the 7-hr-zygote stage, resulting in the methylation of nearly half of the total deoxycytidine residues. The extent of zygotic cpDNA methylation was shown to be dependent on the preexisting methylation level of both parental gametic cpDNAs . L-Ethionine and 5-azacytidine effectively inhibited cpDNA methylation during gametogenesis and ensuing zygotic development as shown by both Hpa II/Msp I digestion patterns and HPLC. The transmission of chloroplast genes was analyzed concomitantly with the inhibitor studies. The two inhibitors produced different patterns of inhibition of methylation in mt- and mt+ cells at a given developmental stage. Our overall results demonstrate that the extent of mating type-specific and gamete-specific methylation during gametogenesis is not correlated with the frequency of maternal transmission of chloroplast genes.
- Published
- 1984
- Full Text
- View/download PDF
176. Effect of L-ethionine on the expression of the SOS system in Escherichia coli.
- Author
-
Barbé J, Castellví M, Vericat JA, and Guerrero R
- Subjects
- DNA Repair radiation effects, Escherichia coli drug effects, Escherichia coli growth & development, Kinetics, Methionine pharmacology, Mutation, Oxygen Consumption drug effects, Temperature, Ultraviolet Rays, DNA Repair drug effects, Escherichia coli genetics, Ethionine pharmacology
- Abstract
The effect of L-ethionine, the ethyl analog of the essential amino acid methionine, on the SOS system of Escherichia coli was studied. This compound does not induce either inhibition of cell division nor cessation of cell respiration in a RecA+ Met+ RelA+ strain, nor in RecA+ Met- RelA+ or RecA+ Met- RelA- mutants. Nevertheless, L-ethionine blocks the expression of both cited SOS functions in a recA441 mutant when it is growing at the restrictive temperature of 42 degrees C. Furthermore, the inhibitory effect of the L-ethionine on the induction of the SOS system in this mutant is increased when the cells are preincubated for several hours in the presence of the analog, before the temperature shift. Moreover, cultures of the recA441 mutant incubated at 42 degrees C in the presence of both L-ethionine and L-methionine present the same behaviour as the cultures of this mutant growing at the same temperature but without either amino acid. On the other hand, L-ethionine does not have any effect on the expression of the two mentioned SOS functions when these are induced by UV-irradiation in a RecA+ strain even if this compound is added to the cells several hours before irradiation.
- Published
- 1984
- Full Text
- View/download PDF
177. Interaction of normal and tumor transfer RNA methyltransferases with ethionine-induced methyl-deficient rat liver transfer RNA.
- Author
-
Kerr SJ
- Subjects
- Animals, Escherichia coli enzymology, Ethionine pharmacology, Female, Kinetics, Liver enzymology, Methylation, Neoplasms, Experimental enzymology, Rats, Carcinoma, Hepatocellular enzymology, Liver Neoplasms enzymology, RNA, Neoplasm, RNA, Transfer, tRNA Methyltransferases metabolism
- Abstract
The tRNA methyltransferases from normal rat liver and Novikoff hepatoma have been compared with respect to their base specificity, capacity to methylate, and reaction kinetics, using mixed Escherichia coli B transfer RNA (tRNA) and ethionine-induced partially methyl-deficient rat liver tRNA. The pattern of base methylation of the two substrates is different with the use of enzymes from either source. In particular, N1-methylguanine methylation is much greater in the methyl-deficient rat liver tRNA. The enzymes from the two sources also show differences in specificity of base methylation in either substrate, particularly in the percentage of N2-methylguanine synthesized. The Novikoff hepatoma enzymes have a greater capacity for methylation with either type of tRNA than do rat liver enzymes. The methyl-deficient rat liver tRNA is a poorer substrate for the enzymes from both sources than is E. coli B tRNA in terms of rate of methylation as well as total acceptance of methyl groups. The affinity constants are somewhat higher for the methyl-deficient rat liver tRNA than for E. coli B tRNA. The Novikoff hepatoma enzymes, in general, have larger affinity constants than the rat liver enzymes. Maximal velocities for the various base-specific enzymes are lower with the methyl-deficient rat liver tRNA, with the exception of the 1-methylguanine specific enzymes. These enzymes from either rat liver or Novikoff hepatoma exhibit approximately a 2.5-fold greater maximal velocity with methyl-deficient rat liver tRNA.
- Published
- 1975
178. Mutagenesis and anti-mutagenesis in Salmonella: influence of ethionine and caffeine on yields of mutations induced by 2-aminopurine and 9-aminoacridine.
- Author
-
MacPhee DG, Nagel BA, and Podger DM
- Subjects
- Mutagenicity Tests, Salmonella typhimurium drug effects, Species Specificity, 2-Aminopurine toxicity, Adenine analogs & derivatives, Aminacrine toxicity, Aminoacridines toxicity, Caffeine pharmacology, Ethionine pharmacology, Mutagens, Mutation
- Abstract
Ethionine, the ethyl analogue of methionine, slightly reduced the yield of reversions of the hisC3076 frameshift marker induced by 9-aminoacridine (9AA) in an excision-proficient strain of Salmonella typhimurium, but completely abolished mutagenesis by 9AA in the excision-deficient uvrB-deletion strain TA1537. No toxic effects of ethionine were apparent in either the excision-proficient or the excision-deficient strain. Because of the differential effects of ethionine on mutagenesis in the two strains, it seemed possible that an ethionine-sensitive step in the process(es) leading to fixation of 9AA-induced mutations might be compensated for by the uvrA,B,C+ excision-repair system. To further test this possibility, we used caffeine (a compound known to significantly reduce the efficacy of the excision-repair process) as a co-treatment with ethionine for cells of an excision-proficient strain exposed to 9AA. Treatment with caffeine alone or ethionine alone had very little effect on reversion yield, whereas co-treatment with the two agents abolished 9AA mutagenesis. It appeared, therefore, that either the caffeine-sensitive pathway or the ethionine-sensitive pathway needed to be functioning if 9AA-induced reversions of hisC3076 marker were to be detected. Addition of methionine to cells of the excision-deficient strain exposed to 9AA restored their ability to be mutated by 9AA, however. In a base-pair substitution back-mutation system, ethionine slightly enhanced the yields of revertants of the trpE8 marker induced by 2-aminopurine (2AP) in both an excision-proficient strain (at all 2AP dose levels tested) and an excision-deficient strain (only at the lower dose levels). In the excision-deficient strain, doses of 2AP above 300 micrograms/plate were highly toxic when ethionine was also present. It was for this reason that no 2AP-induced revertants were recovered at the higher 2AP concentrations. Treatment of the trpE8 strain with methionine also enhanced the yield of 2AP-induced revertants of this marker.
- Published
- 1983
- Full Text
- View/download PDF
179. Isolation of oval cells and transitional cells from the livers of rats fed the carcinogen DL-ethionine.
- Author
-
Sells MA, Katyal SL, Shinozuka H, Estes LW, Sell S, and Lombardi B
- Subjects
- Animals, Bile Canaliculi cytology, Bile Canaliculi drug effects, Bile Ducts cytology, Bile Ducts drug effects, Cell Division drug effects, Cell Fractionation, Cell Separation, Cell Survival, Fluorescent Antibody Technique, Histocytochemistry, Liver cytology, Male, Microscopy, Electron, Rats, Carcinogens pharmacology, Ethionine pharmacology, Liver drug effects
- Abstract
For the characterization of the metabolic and biologic properties of oval cells (i.e., cells emerging in the livers of rats treated with chemical carcinogens due to proliferation of bile ductular and/or duct cells) and transitional cells (i.e., cells having properties intermediate between those of oval cells and hepatocytes), these cells were isolated from the livers of Sprague-Dawley rats fed DL-ethionine for 4-5 weeks. The livers were dissociated into single cells by perfusion in situ with collagenase, and total cell suspensions were allowed to stand at unit gravity for 10 minutes to separate parenchymal (hepatocytes) from nonparenchymal cells. Nonparenchymal cells were centrifuged in linear gradients of Metrizamide (8-24% wt/vol), and 2-ml fractions were collected from the gradients. The cells in the fractions were defined by light microscopy, electron microscopy, and histochemical and immunofluorescence methods. A cell isolate was thus obtained consisting of Kupffer's cells (approximately 20%), bile ductular and/or duct cells and oval cells (approximately 30%), and transitional cells (approximately 50%). A twofold enrichment of bile ductular and/or duct cells and their derivatives was achieved over that found in the nonparenchymal cell fraction before isopyknic gradient centrifugation.
- Published
- 1981
180. Threonine production by ethionine-resistant mutants of Serratia marcescens.
- Author
-
Komatsubara S, Kisumi M, and Chibata I
- Subjects
- Chromosome Mapping, Drug Resistance, Microbial, Genotype, Kinetics, Phenotype, Serratia marcescens drug effects, Serratia marcescens growth & development, Species Specificity, Ethionine pharmacology, Mutation, Serratia marcescens genetics, Threonine biosynthesis
- Abstract
Ethionine reduced both the growth rate and the final growth level of Serratia marcescens Sr41. Growth inhibition was completely reversed by methionine. Strain D-315, defective in homoserine dehydrogenase I, was more sensitive to ethionine-mediated growth inhibition than was the wild-type strain. Ethionine-resistant mutants were isolated from cultures of strain D-316, which was derived from strain D-315 as a threonine deaminase-deficient mutant. Of 60 resistant colonies, 7 excreted threonine on minimal agar plates. One threonine-excreting strain, ETr17, was highly resistant to ethionine and, moreover, insensitive to methionine-mediated growth inhibition, whereas the parent strain was sensitive. When cultured in minimal medium with or without excess methionine, strain ETr17 had a higher homoserine dehydrogenase level than did strain D-316. The homoserine dehydrogenase activity was not inhibited by threonine or methionine. Transductional analysis revealed that the ethionine-resistant (etr-1) mutation carried by strain ETr17 was located in the metBM-argE region and caused the derepressed synthesis of homoserine dehydrogenase II. Strain ETr17 had a higher aspartokinase level than did the parent strain. By transductional cross with the argE+ marker, the etr-1 mutation was transferred into strain D-562 which was derived from D-505, a strain defective in aspartokinases I and III. The constructed strain had a higher aspartokinase level than did strain D-505 in medium with or without excess methionine, indicating that the etr-1 mutation led to the derepressed synthesis of aspartokinase II. Strain ETr17 produced about 8 mg of threonine per ml of medium containing sucrose and urea.
- Published
- 1983
- Full Text
- View/download PDF
181. Ethionine-resistant mutants of the filamentous blue-green alga Plectonema boryanum.
- Author
-
Hentschel WM, Farmer JL, and Andersen WR
- Subjects
- Cyanobacteria genetics, Cyanobacteria metabolism, Drug Resistance, Microbial, Ethionine metabolism, Genes, Methionine metabolism, Mutation, Cyanobacteria drug effects, Ethionine pharmacology
- Abstract
Plectonema boryanum mutants that are resistant to ethionine are unable to incorporate ethionine into acid-precipitable material. Ethionine causes bleaching of chlorophyll in sensitive cells.
- Published
- 1978
- Full Text
- View/download PDF
182. [Effect of parathyroid hormone on ulcerogenesis (author's transl)].
- Author
-
Kuratsuka H
- Subjects
- Animals, Ethionine pharmacology, Hematoxylin pharmacology, Histamine pharmacology, Male, Rats, Gastric Mucosa drug effects, Parathyroid Hormone pharmacology, Stomach Ulcer chemically induced
- Published
- 1977
183. Effect of dietary DL-ethionine and/or DL-methionine on egg laying and activities of some cytoplasmic NAD linked-dehydrogenases and NADPH-producing enzymes in liver of Japanese quail, Coturnix coturnix japonica.
- Author
-
Yamada M
- Subjects
- Animals, Carbohydrate Metabolism, Cytoplasm enzymology, Drug Synergism, Female, Glucosephosphate Dehydrogenase metabolism, Glycerolphosphate Dehydrogenase metabolism, Isocitrate Dehydrogenase metabolism, L-Lactate Dehydrogenase metabolism, Lipid Metabolism, Malate Dehydrogenase metabolism, NAD, Phosphogluconate Dehydrogenase metabolism, Alcohol Oxidoreductases metabolism, Coturnix physiology, Ethionine pharmacology, Liver enzymology, Methionine pharmacology, NADP metabolism, Oviposition drug effects, Quail physiology
- Abstract
The effect of dietary DL-ethionine and/or DL-methionine on egg laying, and activities of some NAD linked-dehydrogenases and NADPH-producing enzymes in liver of Japanese quail, Coturnix coturnix japonica was investigated. A 0.30% DL-ethionine plus 0.30% DL-methionine supplemented diet reversed partially the egg laying inhibited by the diet with 0.30% DL-ethionine alone. No inhibitory effect on egg laying was observed for the diet supplemented with 0.30% DL-methionine alone. In marked contrast to the decreased activity of L-glycerol 3-phosphate dehydrogenase and malate dehydrogenase, significantly increased activity of lactate dehydrogenase was obtained for quail fed the DL-ethionine, and the DL-ethionine plus the DL-methionine supplemented diet, respectively. No marked changes in activities of these three dehydrogenases were obtained for quail fed the diet supplemented with DL-methionine alone. Although decreased activity was observed for all of the four NADPH-producing enzymes in quail fed the diet supplemented with DL-ethionine alone, the DL-ethionine plus DL-methionine, the smallest decrease was obtained for NADP-isocitrate dehydrogenase. The diet supplemented with DL-methionine alone induced markedly the respective activity of malic enzyme and glucose 6-phosphate dehydrogenase. These results indicate a relatively important function of NADP-isocitrate dehydrogenase for NADPH-production even under DL-ethionine toxicity and suggest complicated relationships between egg production and activities of enzymes associated with carbohydrate and lipid metabolism in quail liver.
- Published
- 1977
- Full Text
- View/download PDF
184. Alteration of methylation patterns in rat liver histones following administration of ethionine, a liver carcinogen.
- Author
-
Cox R and Tuck MT
- Subjects
- Animals, Arginine metabolism, Cell Nucleus analysis, Histone-Lysine N-Methyltransferase analysis, Lysine metabolism, Male, Methionine pharmacology, Methylation, Protein-Arginine N-Methyltransferases analysis, Rats, Ethionine pharmacology, Histones metabolism, Liver metabolism
- Abstract
The possible role of alterations of histone methylation by ethionine in the mechanism of ethionine carcinogenesis was studied. In regenerating rat liver, histone synthesis was inhibited by only 20 to 30% with large doses of ethionine (0.75 to 1.0 mg/g body weight). The effect of ethionine on the in vivo methylation of histones was studied by giving 0.5 mg ethionine and [methyl-3H]methionine per g body weight. In vivo methylation of lysine was inhibited by 50%, whereas the arginine methylation was inhibited by 89%. The cellular localization of the methyltransferases and S-adenosyl-L-ethionine may be related to this differential effect. Utilizing an in vitro assay for protein-lysine and protein-arginine methyltransferases, we have demonstrated that the methyl-deficient histones are transported to the nucleus and with time lose their ability to accept methyl groups in vitro.
- Published
- 1981
185. Induction of thymidine kinase in enzyme-deficient Chinese hamster cells.
- Author
-
Harris M
- Subjects
- Animals, Azacitidine pharmacology, Butyrates pharmacology, Cell Differentiation drug effects, Cells, Cultured, Cricetinae, Cricetulus, DNA metabolism, Enzyme Induction drug effects, Ethionine pharmacology, Ethyl Methanesulfonate pharmacology, Gene Expression Regulation drug effects, Methylation, Thymidine Kinase metabolism, Thymidine Kinase biosynthesis
- Abstract
Previous work with Chinese hamster cells suggests that thymidine kinase deficiency and loss of potential for plating in HAT medium may arise by a process of mutation coupled with site-specific repression by bromodeoxyuridine at the tk locus. In this study, tk- Chinese hamster cells were exposed to a series of inductors to determine whether revertants for the putative second stage originate by genetic or epigenetic change. Brief exposure to 5-azacytidine resulted in massive conversion to the HAT+ state, and revertants showed levels of thymidine kinase activity intermediate between those of tk- and wild-type cells. By contrast, incidence of HAT+ cells rose only slightly in populations mutagenized with ethyl methanesulfonate. Large increases in frequency of HAT+ cells were obtained by treatment with n-butyrate and L-ethionine, which affect gene expression in other cell systems but have no known mutagenic potential. Induction of HAT+ revertants seems to be mediated by a stable epigenetic shift, which reverses the gradual extinction of thymidine kinase activity in the parent cells. The data support the view that induction in Chinese hamster cells results from changes in DNA methylation patterns, and suggests studies to define the process in molecular terms.
- Published
- 1982
- Full Text
- View/download PDF
186. Effects of ethionine feeding on fatty liver and plasma lipoprotein fractions in rats.
- Author
-
Yokota F, Igarashi Y, and Suzue R
- Subjects
- Animals, Cholesterol blood, Diet, Fatty Acids, Nonesterified blood, Female, Male, Phosphatidylcholine-Sterol O-Acyltransferase blood, Rats, Rats, Inbred Strains, Sex Factors, Ethionine pharmacology, Fatty Liver chemically induced, Lipoproteins blood
- Abstract
We studied the changes in the lipid metabolism of rats fed a 0.5% DL-ethionine-containing diet. On day 3, hepatic lipid and cholesterol were markedly elevated in male and female rats; their plasma total cholesterol and plasma lecithin cholesterol acyltransferase (LCAT) activity levels were lower than in the controls. On day 7 and 14, hepatic lipid and cholesterol were near the control level, while plasma cholesterol and LCAT activity, especially in male rats, were higher than in the controls. Electrophoresis of the plasma lipoprotein complexes revealed a progressive decrease of the alpha fraction, irrespective of sex. These DL-ethionine-induced changes may be due to changes in hepatic adenosine triphosphate levels leading to the inhibition of protein biosynthesis.
- Published
- 1982
- Full Text
- View/download PDF
187. Time dependence of ethionine-induced changes in rat liver transfer RNA methylation.
- Author
-
Wainfan E, Tscherne JS, Maschio FA, and Balis ME
- Subjects
- Adenine metabolism, Adenine pharmacology, Animals, Cytosine metabolism, Drug Interactions, Female, Guanine metabolism, Liver drug effects, Liver enzymology, Methylation, Rats, S-Adenosylmethionine pharmacology, Uracil metabolism, tRNA Methyltransferases metabolism, Ethionine pharmacology, Liver metabolism, RNA, Transfer metabolism
- Abstract
Methyl-deficient transfer RNA (tRNA) and subnormal levels of tRNA-methylating enzymes were found in the livers of female rats that had received injections of 250 mg DL-ethionine per kg body weight per day and 120 mg adenine per kg body weight per day for 2 days. Adenine alone had no effect. When the ethionine plus adenine injections were continued for longer periods of time, liver tRNA-methylating enzyme activity measured in vitro gradually increased and exceeded that of the controls. Concurrently, the relative methyl deficiency of liver tRNA decreased. The latter was evident because of the decreased ability of the tRNA to accept methyl groups during in vitro methylation catalyzed by homologous enzymes. Liver tRNA from animals that were treated with ethionine for 7 days could accept only about 40% as many methyl groups as could tRNA from animals that had received ethionine for only 2 days. No further significant change in methyl deficiency of the tRNA was seen when ethionine administration was extended to a total of 14 days. Enzyme preparations from ethionine-treated, but not control, rat livers contained dialyzable substances that inhibited the tRNA methylases and altered the base specificity of these enzymes. Although S-adenosylhomocysteine and S-adenosylethionine were found to be present in the liver preparations, neither of these substances could account for the observed changes in specificity.
- Published
- 1977
188. The effect of egg phospholipid administration upon liver enzymic activities during ethionine treatment.
- Author
-
Montanini I, Fratini F, and Porcellati G
- Subjects
- Adenosine Triphosphatases metabolism, Animals, Female, Glucose-6-Phosphatase metabolism, NADPH-Ferrihemoprotein Reductase metabolism, Phospholipids administration & dosage, Rats, Eggs, Ethionine pharmacology, Liver enzymology, Phospholipids pharmacology
- Abstract
Female rats were injected subcutaneously with ethionine, and enzymic activities of liver membranes (Na+-k+-stimulated ATPase, Mg2+-stimulated ATPase, glucose-6-phosphatase, NADPH: cytochrome c oxido-reductase and NAD-nucleosidase) examined at proper intervals, during the intraperitoneal treatment of an egg phospholipid preparation (EPL). It is shown that EPL is unable to overcome the enzymic changes due to severe ethionine treatment, but is able to facilitate the recovery times after drug withdrawal for all the enzymic activities, except for NAD-nucleosidase. At lower dosage of the drug, the ethionine treatment is able to prevent the observed change of the glucose-6-phosphatase activity but not that of the Mg2+-ATPase. It is suggested that the EPL treatment may modify the chemical composition ahd/or architecture of liver membranes, altered by the ethionine injection, thus acting, at least partially, on the enzymic changes.
- Published
- 1976
189. Cleavage of virus-specified polypeptides in cells infected with Semliki Forest Virus.
- Author
-
Morser MJ and Burke DC
- Subjects
- Amino Acids analysis, Animals, Aza Compounds pharmacology, Azetines pharmacology, Butanols pharmacology, Canavanine pharmacology, Cell Line, Chick Embryo, Cricetinae, Ethionine pharmacology, Fluorides pharmacology, Glucosamine pharmacology, Glycoproteins biosynthesis, Hemagglutinins, Viral, Isoflurophate pharmacology, Kidney, Protease Inhibitors, RNA, Viral biosynthesis, Tosyl Compounds pharmacology, Tryptophan pharmacology, Viral Proteins biosynthesis, Peptides analysis, Semliki forest virus
- Published
- 1974
- Full Text
- View/download PDF
190. Effect of dietary DL-ethionine on egg laying and activities of cytoplasmic and mitochondrial L-glycerol 3-phosphate dehydrogenases in liver and kidney of Japanese quail, Coturnix coturnix japonica.
- Author
-
Yamada M
- Subjects
- Animals, Cytoplasm enzymology, Female, Kidney enzymology, Liver drug effects, Liver enzymology, Mitochondria enzymology, Mitochondria, Liver enzymology, Succinate Dehydrogenase antagonists & inhibitors, Coturnix physiology, Ethionine pharmacology, Glycerolphosphate Dehydrogenase antagonists & inhibitors, Oviposition drug effects, Quail physiology
- Abstract
The effect of dietary DL-ethionine on egg laying and activities of succinate dehydrogenases, cytoplasmic and mitochondrial L-glycerol 3-phosphate dehydrogenases, in liver and kidney of Japanese quail, Coturnix coturnix japonica was investigated. When quail at full laying were fed a diet supplemented with DL-ethionine at 0.05%, 0.10%, 0.15% and 0.30% (w/w), respectively, apparent DL-ethionine concentration dependent inhibitions of egg laying rate, weights of ovary and oviduct, and egg weight were observed. At the 0.30% level, activity per g tissue of cytoplasmic L-glygerol 3-phosphate dehydrogenase from liver and kidney decreased to about one-half of the initial activity. A significant difference in the activity of mitochondrial L-glycerol 3-phosphate and succinate dehydrogenase from liver and kidney was obtained between the control and the DL-ethionine fed quail, respectively. These results indicated that dietary DL-ethionine inhibits egg laying and activities of L-glycerol 3-phosphate dehydrogenases and succinate dehydrogenase of both liver and kidney of Japanese quail.
- Published
- 1977
- Full Text
- View/download PDF
191. Lysine transfer RNA2 is the major target for L-ethionine in the rat.
- Author
-
Kuchino Y, Sharma OK, and Borek E
- Subjects
- Animals, Ethionine pharmacology, Female, Lysine, Molecular Weight, Oligoribonucleotides analysis, Rats, Ethionine metabolism, Liver metabolism, RNA, Transfer metabolism
- Abstract
Ethionine, a hepatocarcinogen, ethylates macromolecules in vivo especially tRNA of rat liver. When rats were injected with L-[ethyl-3H]ethionine, the tRNA fraction of the liver was found to be labeled. One tRNA with the highest specific activity was purified and identified as lysine-tRNA2.
- Published
- 1978
- Full Text
- View/download PDF
192. Reversal of the ethionine-induced inhibition of rat liver ribonucleic acid polymerases in vivo by adenine.
- Author
-
Farber JL, Shinozuka H, Serroni A, and Farmar R
- Subjects
- Animals, Carbon Radioisotopes, Cell Nucleus metabolism, Chromatography, DEAE-Cellulose, Cycloheximide pharmacology, DNA, DNA-Directed RNA Polymerases biosynthesis, DNA-Directed RNA Polymerases isolation & purification, Depression, Chemical, Female, Leucine metabolism, Liver drug effects, Liver metabolism, Liver ultrastructure, Methionine pharmacology, Mycotoxins, Oligopeptides, Orotic Acid metabolism, Peptides, Cyclic, RNA biosynthesis, Rats, Solubility, Tritium, Adenine pharmacology, DNA-Directed RNA Polymerases antagonists & inhibitors, Enzyme Inhibitors, Ethionine pharmacology, Liver enzymology
- Published
- 1974
193. Nuclear metabolism of ribosomal RNA in growing, methionine-limited, and ethionine-treated HeLa cells.
- Author
-
Wolf SF and Schlessinger D
- Subjects
- Cell Nucleus drug effects, Half-Life, HeLa Cells drug effects, Kinetics, Methionine pharmacology, Neoplasm Proteins biosynthesis, Protein Biosynthesis, RNA, Neoplasm metabolism, Cell Nucleus metabolism, Ethionine pharmacology, HeLa Cells metabolism, Methionine metabolism, RNA, Ribosomal metabolism
- Published
- 1977
- Full Text
- View/download PDF
194. The influence of ethionine on the phosphorylation state of adenine nucleotides in isolated hepatocytes.
- Author
-
Lavoinne A, Marchand JC, Pinosa M, and Matray F
- Subjects
- Animals, Female, Glucose metabolism, In Vitro Techniques, Liver drug effects, Oxidation-Reduction, Phosphates metabolism, Phosphorylation, Rats, Rats, Inbred Strains, Adenine Nucleotides metabolism, Ethionine pharmacology, Liver metabolism
- Abstract
The influence of D,L-ethionine (5 mM) was tested on hepatocytes isolated from fed or fasted rats. The digitonine fractionation procedure [6] was used to determine the repartition of adenine nucleotides and inorganic phosphate. Ethionine induces a decrease in the intracellular ATP content; this decrease is located both in the cytosol and in the mitochondria of fed and fasted rat hepatocytes. The observed effects of ethionine are: 1) fed rats: increase in glycolysis, decrease in mitochondrial ATP/ADP x PO4 and mitochondrial NAD+/NADH ratios; 2) fasted rats: decrease in neoglucogenesis from lactate + pyruvate or alanine, decrease in cytosolic ATP/ADP x PO4 and cytosolic NAD/NADH ratios.
- Published
- 1983
- Full Text
- View/download PDF
195. Sister chromatid exchanges induced by DNA demethylating agents persist through several cell cycles in mammalian cells.
- Author
-
Perticone P, Cozzi R, and Gustavino B
- Subjects
- Animals, Cells, Cultured, Cricetinae, Cricetulus, Humans, Methylation, Mitomycin, Mitomycins pharmacology, Ultraviolet Rays, Azacitidine pharmacology, Cell Cycle, DNA metabolism, Ethionine pharmacology, Sister Chromatid Exchange
- Abstract
Eukaryotic DNA methylation has been extensively studied in recent years. The ability of many carcinogens to interfere with DNA methylation has not yet been directly related to their tumorigenic activity. Recent data obtained using L-ethionine and 5-azacytidine--both demethylating agents--showed a small but significant increase in the sister chromatid exchange (SCE) rate induced in mammalian cells (human lymphocytes and CHO cells). In this paper we show that the SCE increase induced by both these agents in Chinese hamster ovary (CHO) cells persists for as long as 10 cell cycles. On the other hand mitomycin-C and u.v. light-induced SCEs show a rapid decrease to the control value, as reported for all known SCE inducers. We suggest that DNA demethylation and SCEs are connected through a perturbation of the cell machinery at the level of the replication fork, producing an increase of the error-prone ligation. Since the methylation level is maintained (inherited), the SCE increase produced by these recombinational events will not be corrected through several cell cycles.
- Published
- 1987
- Full Text
- View/download PDF
196. Methyldeficient mammalian 4s RNA: evidence for L-ethionine-induced inhibition of N6-dimethyladenosine synthesis in rat liver tRNA.
- Author
-
Wildenauer D and Gross HJ
- Subjects
- Adenosine analogs & derivatives, Adenosine metabolism, Animals, Base Sequence, Carbon Radioisotopes, Chromatography, Paper, Chromatography, Thin Layer, Female, Isomerism, Liver drug effects, Mass Spectrometry, Methanol, Methylation, Oligonucleotides analysis, Rats, Ribonucleases, Spectrophotometry, Ultraviolet, Time Factors, Ethionine pharmacology, Liver metabolism, RNA, Transfer biosynthesis, Transcription, Genetic drug effects
- Abstract
The nucleotide composition of 4s RNA from livers of rats fed with a diet containing 0.3% D-ethionine was found to be identical with that from untreated animals. In contrast, one single modified nucleotide was absent in 4s RNA from livers of rats fed with a 0.3% L-ethionine diet. The minor nucleo=tide was also absent in liver 4s RNA from rats fed with a 0.3% L-ethionine diet followed by ten days of normal food. It was identified after dephosphorylation by ultraviolet absorption spectra, cochromatography with authentic material and mass spectra as N(6)-dimethyladenosine. It is concluded that S-adenosylethionine, the primary product of L-ethionine in the liver, causes strong and selective inhibition of the specific RNA-methylase responsible for adenosine to N(6)-dimethyl=adenosine methylation in rat liver 4s RNA. Compared to the strong inhibition of N(6)-dimethyladenosine formation described here, L-ethionine-dependent ethylation of liver 4s RNA is far less efficient. The quantitation of l-methyladenosine, ribothymidine and 3'-terminal adenosine in this 4s RNA as well as its aminoacid acceptor activity is typical for tRNA; hence it may be concluded that N(6)-dimethyladenosine is a component of rat liver tRNA. This may demonstrate the first evidence for the existence of specifically methyl-deficient mammalian tRNA. A possible correlation between the activity of L-ethionine as a liver carcinogen and its ability to induce the formation of methyl-deficient tRNA by selectively inhibiting the synthesis of N(6)-dimethyladenosine on the tRNA level in the same organ is discussed.
- Published
- 1974
- Full Text
- View/download PDF
197. Changes in peroxisomes and mitochondria in liver of ethionine exposed rats: a biochemical and morphological investigation.
- Author
-
Aarsaether N, Aarsland A, Kryvi H, Nilsson A, Svardal A, Ueland PM, and Berge RK
- Subjects
- Acid Phosphatase metabolism, Animals, Catalase metabolism, Dose-Response Relationship, Drug, Glutamate Dehydrogenase metabolism, L-Lactate Dehydrogenase metabolism, Liver drug effects, Liver ultrastructure, Male, Microbodies drug effects, Microbodies ultrastructure, Mitochondria, Liver drug effects, Mitochondria, Liver ultrastructure, NADPH-Ferrihemoprotein Reductase metabolism, Rats, Rats, Inbred Strains, Reference Values, Urate Oxidase metabolism, Ethionine pharmacology, Liver enzymology, Microbodies enzymology, Mitochondria, Liver enzymology
- Abstract
Administration of ethionine resulted in a dose- and time-dependent enhancement of the activities of peroxisomal beta-oxidation, carnitine palmitoyltransferase and omega-oxidation, especially the 12-hydroxylation of lauric acid. The mitochondrial and, especially, the microsomal palmitoyl-CoA hydrolase activities were increased, whereas the peroxisomal and cytosolic activities were decreased. Ethionine administration decreased the catalase and urate oxidase activities in both a dose- and time-related manner. The liver cells and the volume fraction of cytoplasma decreased 40% in ethionine-exposed animals, whereas the average nuclei volume fraction increased approximately 50%. The volume fraction and the total number of mitochondria increased 1.5-fold after ethionine exposure and an accumulation of lipid in large droplets of the hepatocytes was observed. No proliferation of peroxisomes was observed after treatment; the volume fraction and the number of peroxisomes decreased. However, the size of peroxisomes in livers of ethionine-exposed rats tended to be greater than controls; a 1.5-fold increase in average size was observed. As there was no induction of the protein content of the bifunctional enoyl-CoA hydratase, an enzyme involved in peroxisomal beta-oxidation, it is considered that ethionine selectively stimulates the peroxisomal beta-oxidation due to increased peroxisome surface area rather than evoked a peroxisome proliferation capacity. Increased peroxisomal beta-oxidation was also observed in the kidney of ethionine-exposed rats at a dose of 750 mg/day/kg body weight. At that dose the amount of reduced glutathione (GSH) was significantly increased in kidney. The amount of GSH and the level of peroxisomal beta-oxidation were significantly increased in liver at an ethionine dose of 100 mg/day/kg body weight. These responses in liver were evident within 2 days of ethionine exposure and then leveled off whereas a significant increase in GSH and peroxisomal beta-oxidation in kidney was observed within 12 days. Whether the acute H2O2-generating peroxisomal oxidation of long-chain fatty acids in the liver may also make this organ susceptible to the long-term effects of low-dose ethionine and be an important step in the chain of events which eventually results in tumour development should be considered.
- Published
- 1989
- Full Text
- View/download PDF
198. The influence of ethionine-supplemented soy protein diet on cell-mediated and humoral immunity.
- Author
-
Radix PM, Walters CS, and Adkins JA
- Subjects
- Animals, Dietary Proteins administration & dosage, Dinitrofluorobenzene immunology, Erythrocytes immunology, Ethionine administration & dosage, Female, Hypersensitivity, Delayed, Lipopolysaccharides pharmacology, Male, Mice, Mice, Inbred C57BL, Mitogens pharmacology, Plant Proteins administration & dosage, Sheep immunology, Glycine max, T-Lymphocytes immunology, Antibody Formation drug effects, Ethionine pharmacology, Immunity, Cellular drug effects
- Abstract
These studies were designed to investigate the influence of ethionine, a suspected carcinogen, on cell-mediated (CMI) and humoral immunity. It is believed that ethionine, an analog of methionine which is produced by intestinal bacteria, could have significant relevance to health. To study the effect of ethionine on immune responsiveness, three groups of mice were allowed to feed ad libitum for 5 weeks on one of the following regimens: diet 1, a basal diet of 16% soy protein; diet 2, soy protein supplemented with 0.6% dl-methionine; and diet 3, soy protein supplemented with 0.1% dl-ethionine. The immunological parameters measured were responsiveness to mitogens, [phytohemagglutinin (PHA), concanavalin A (Con A), pokeweed mitogen (PWM), and lipopolysaccharide (LPS)], delayed-type hypersensitivity (DTH) to dinitrofluorobenzene (DNFB), and antibody formation to sheep red blood cells (SRBC). There were no significant differences in mitogen and antigen responses in mice maintained on diets 1 and 2 as measured by thymidine uptake in proliferating lymphocytes. However, there was a significant suppression in mitogen responsiveness in mice that received diet 3. DTH was also suppressed in mice on diet 3. Antibody levels were similar in all groups. Thus, there was clear evidence of suppression of CMI by ethionine in these studies.
- Published
- 1983
- Full Text
- View/download PDF
199. Enhanced repair of O6-methylguanine in liver DNA of rats pretreated with phenobarbital, 2,3,7,8-tetrachlorodibenzo-p-dioxin, ethionine, or N-alkyl-N-nitrosoureas.
- Author
-
Den Engelse L, Floot BG, Menkveld GJ, and Tates AD
- Subjects
- Alkylation, Animals, DNA metabolism, Guanine metabolism, Male, Methionine pharmacology, Rats, Rats, Inbred Strains, DNA Repair drug effects, Dioxins pharmacology, Ethionine pharmacology, Guanine analogs & derivatives, Liver metabolism, Nitrosourea Compounds pharmacology, Phenobarbital pharmacology, Polychlorinated Dibenzodioxins pharmacology
- Abstract
Rats were pretreated for a number of weeks with the liver tumour promoters phenobarbital and 2,3,7,8-tetrachlorodibenzo-p-dioxin, the direct alkylating agents N-ethyl-N-nitrosourea and N-methyl-N-nitrosourea, and the hepatocarcinogens ethionine and diethylnitrosamine. A subsequent challenge with a single, low dose of radioactively labelled dimethylnitrosamine was given to assay the capacity of the liver for O6-methylguanine repair. Pretreatment with 0.05% phenobarbital in the diet for 8 weeks (a promoting regimen) resulted in significantly enhanced O6-methylguanine repair; shorter pretreatment periods (3 days or 2 weeks) had no significant effect. Repeated injection of another liver tumour promoter, 2,3,7,8-tetrachlorodibenzo-p-dioxin, also resulted in enhancement of O6-methylguanine repair. Pretreatment for 2 weeks with N-ethyl-N-nitrosourea resulted in strongly enhanced O6-methylguanine repair, as did a similar pretreatment with diethylnitrosamine, which was included as a positive control. The same pretreatment scheme which was highly effective in the case of N-ethyl-N-nitrosourea, was found to be totally ineffective in the case of N-methyl-N-nitrosourea. When N-methyl-N-nitrosourea was administered for 8 weeks instead of 2, a small but statistically significant increase in O6-methylguanine repair was observed. It is concluded that two factors are responsible for the low effectivity of N-methyl-N-nitrosourea. The first is the relatively low extent of liver DNA methylation by this compound when compared with dimethylnitrosamine. The second is the low efficiency of methylating agents (expressed per extent of DNA alkylation) to induce O6-methylguanine repair in rat liver when compared with ethylating agents. Pretreatment for 2 weeks with a diet containing DL-ethionine also resulted in a substantially increased O6-methylguanine repair capacity. Neither this enhancement, nor that induced by a pretreatment with diethylnitrosamine, could be inhibited by simultaneous feeding of a methionine-enriched diet. Our results indicate that neither increased hepatocellular proliferation nor direct interaction with DNA are necessary for the induction of O6-methylguanine repair enhancement. It is concluded that the capacity of an agent to enhance O6-methylguanine repair in rat liver reflects the hepato(co)carcinogenic capacity of that agent.
- Published
- 1986
- Full Text
- View/download PDF
200. Bile acid metabolism in mammals. VI. Effect of ethionine upon bile acids of rat bile.
- Author
-
Kakis G, Fisher MM, and Yousef IM
- Subjects
- Animals, Bile drug effects, Catheterization, Chenodeoxycholic Acid metabolism, Cholic Acids metabolism, Chromatography, Gas, Chromatography, Thin Layer, Deoxycholic Acid metabolism, Female, Lithocholic Acid metabolism, Male, Rats, Sex Factors, Bile metabolism, Bile Acids and Salts metabolism, Ethionine pharmacology
- Published
- 1974
- Full Text
- View/download PDF
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.