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Ionizing radiation-induced dominant lethal mutations in all spermatogenic stages. After irradiation of male mice with 200 R the yield of induced mutations in early spermatids was twice the yield in spermatozoa, late spermatids, and spermatocytes. After irradiation with 400 R or 800 R the spermatocytes were the most sensitive stage for the induction of dominant lethal mutations. The frequency of radiation-induced dominant lethal mutations in postspermatogonial stages was dose-dependent. The yield of dominant lethal mutations in spermatogonia was independent of the dose. Pretreatment with chloramphenicol enhanced the frequency of radiation-induced dominant lethal mutations only in spermatozoa. Pretreatment with S,2-aminoethylisothiuronium · Br · HBr (AET) reduced the frequency of radiation-induced dominant lethal mutations in early spermatids. Chemically mutagens can be characterized by their stage-specific induction of mutations. The straight chain alkyl methanesulfonates ethyl methanesulfonate (EMS), methyl methanesulfonate (MMS) and n-propyl methanesulfonate (PMS) induced a high frequency of dominant lethal mutations in spermatozoa and late spermatids. The induced dominant lethal mutation rate decreased to the control level of embryonic lethality in early spermatids. No mutations were induced in spermatocytes. The absence of induced mutations in spermatozoa and late spermatids was typical for the spermatogenic response after treatment with mytomycin C. Mutations were induced in early spermatids. Spermatocytes were the most sensitive germ-cell stage for the induction of dominant lethal mutations with mitomycin C. Possible explanations for the differential spermatogenic response to radiation- and chemically-induced dominant lethal mutations are discussed.

It has been shown that when 32P counting from a tumour is continuous peaks in the count rate can sometimes be induced by large doses of nicotinic acid, nicotinic acid, nicotinamide or 3-acetylpyridine, but not by 6-aminonicotinamide. These 32P counting peaks have been associated with the time of maximal new synthesis of nicotinamide adenine dinucleotide (NAD). Sensitization to irradiation or some cytotoxic drugs has been found at the peak of this new NAD synthesis. The radioprotective agents cysteamine, 2-aminoethylisothiouronium bromide (AET) and serotonin have been found to cause a rapid fall in tissue NAD levels. The results have been briefly discussed. ImagesFigs. 3

Red cells incubated with N-acetylcysteine or D-penicillamine in appropriate concentrations become sensitive to lysis by acidified normal human serum, i.e. become PNH-like cells and give a positive Ham test. At the same time the cells lose some of their acetylcholinesterase activity. Substances active in this way share a common chemical grouping

The effect of disintegration of incorporated 32P atoms on the functional survival of different viral cistrons was investigated by infecting non-permissive host bacteria jointly with a non-radioactive rII or am T4 mutant and with highly 32P-labeled T4 am+ wild-type phage, and then following upon radioactive decay the loss of ability of the wild type to complement growth of the conditionally lethal mutant phage in the same cell. These experiments showed that the function of each of eleven different viral cistrons is abolished by 32P decay at about half the rate of loss of viability of the whole phage. The relative 32P decay sensitivity of one-half cannot represent the functional inactivation of about half of the viral genome by each lethal 32P disintegration, since the ability of the wild-type phage to complement a variety of am double mutants is lost only slightly faster than, and never at twice, the rate of loss of complementation of single am mutants. Nevertheless, the sensitivity of multiple cistron function does increase as more and more am mutant cistrons are brought into play, until in the case of complementation of a sextuple am mutant, joint functional survival of six cistrons is lost at 0.8 the rate of loss of viability of the whole am+ phage. These observations can be interpreted by postulating two types of lethal 32P disintegrations, long-range hits that cause functional inactivation of the whole, and short-range hits that inactivate only part of the viral genome. Analysis of the results from this point of view shows that about half of the lethal 32P hits are of the short-range type if decay proceeds either at −196°C or at + 4°C. The frequency of short-range hits is sharply reduced, however, if the free radical trap AET‡ is present during decay at 4°C, suggesting that short-range hits represent radiochemical lesions, in the production of which free radicals play an important part. Calculation of the fraction of all 32P disintegrations that inactivates a given cistron by short-range hits shows that this fraction is equal to about half the total share of the whole genome represented by that cistron. This coincidence leads to the notion that half the 32P disintegrations occurring within the confines of a viral cistron produce sub-lethal damage preventing its functional expression, unless the damage had first been erased by a repair process which can proceed in the infected cell. Short-range hits would then correspond to lesions in the viral DNA that render non-erasable, and thus permanently fix, all sublethal cistron damages that have already occurred, or may yet occur, upon further decay.

SummarySeven radioprotective agents have been tested for their ability to protect the mouse against three radiation-induced modes of death. Six of the seven agents offer relatively less protection against gastrointestinal death than against haematopoietic death, and only one (PAPP) is effective against CNS death. It is proposed that the variations in protection against the three forms of death may be the result of tissue-specific differences in the ability to concentrate and respond to each agent.

The effect of five different reactions which activate complement (antibody activation, reduction in ionic strength, acidification, cobra venom factor (CoF) activation, and inulin activation) upon normal and PNH cells was investigated, using normal serum and serum devoid of the fourth component of complement (C4) activity from patients with hereditary angioneurotic edema (HANE) as a source of complement. Both normal and HANE serum lysed paroxysmal nocturnal hemoglobinuria (PNH) cells when complement was activated by acidification, CoF and inulin, indicating that the terminal steps of complement were activated in the absence of C4, presumably by the alternate or properdin pathway. Normal but not HANE serum lysed cells coated with anti-I, indicating that complement was activated by the C1-dependent classic pathway. HANE serum partially supported lysis by serum at reduced ionic strength, indicating that the activation of terminal complement components had occurred through both of the pathways of activation. The amount of the third component of human complement (C3) which was bound to the membrane of lysed and unlysed cells by these procedures was determined by anti-C3 absorption and was found to differ for each method of complement activation. In general, more C3 was bound to lysed cells than to unlysed cells. For given conditions, more was bound to PNH cells than to normal cells. However, very much less bound C3 was required for lysis of the PNH cells than for lysis of normal cells. These two phenomena, especially the latter, account for the marked lysis of PNH cells when complement is activated. Normal cells treated with AET (aminoethylisothiouronium bromide) did not bind more C3 than untreated cells and the lysed cells had less bound C3 than lysed PNH cells.

SummaryThe radioprotective effect of eight thiol compounds with pK-values of their thiol groups varying from 8·5–10·8 was tested on isolated cells in vitro. The influence of variations in pH of the incubation medium between 6·3 and 8·3 was investigated. The ability of the cells to form colonies was used as the criterion for survival.By comparing the protection affected by different concentrations of the various compounds it was found that a good correlation existed between the degree of radio-protection and the thiolate concentration in the medium. This correlation was also found to be present under anoxic conditions. It was concluded that the increase of the radio-protective activity of the thiol compounds, caused by an increase of either concentration, pH or temperature, can be explained by an increase of the amount of thiol compound present inside the cell. The differences in radio-protective activity of the various compounds cannot be explained by differences in cellular uptake.The thiol compounds wit...

SummaryThe response of the stem cells of the duodenal mucosa in mice protected with AET or with a mixture of radioprotectors and exposed to 225 R of x-rays was studied. Under these conditions the protective action observed in the stem cells of the duodenum is partially masked by the biochemical shock that follows the administration of these chemicals. For the four end-points studied, a protective effect was observed only for the number of nuclei per crypt and the number of pycnotic and karyorrhectic nuclei.

Proton radiation is currently employed in a few centers in the United States and Sweden for the treatment of brain tumors in man. There is, however, relatively little quantitative information in the literature on the radiobiological response of experimental brain tumors. Some studies of x-radiation effects on gliomas in mice have been reported (1–3), but the difficulties associated with the use of intracerebral tumors led us to choose a subcutaneously transplantable ependymoma. This test system is a highly malignant neoplasm which transplants readily and grows rapidly. In the normal routine sequential transplants over several years, 100 per cent tumor growth has been obtained (4). We have investigated the in vivo response of this tumor to x and proton radiation under a variety of conditions, in terms of reduction in successful transplantation immediately after irradiation of the tumor-bearing animal. Materials and Methods The two mouse gliomas (Nos. 15 and 48) which we have studied had been induced in C3H...

Aqueous solutions of creatine phosphokinase are inhibited by Co/sup 60/ gamma radiation. A G value of 0.47 was obtained with an enzyme concentration of 1.7 x 10/sup -6/ M. Protection against gamma radiation was obtained with S-(2- aminoethyl)isothiuronium (AET) salts. A protective mechanism involving a shielding linkage with biological molecules is suggested. (auth)

Summary. In paroxysmal nocturnal haemoglobinuria (PNH) the intensity of haemolysis obtained in the acidified-serum and sucrose-haemolysis tests—the two procedures most commonly used for the laboratory diagnosis of the disease—varies according to the red cells, serum and test used. The influence of these three variables has been investigated on both PNH and PNH-like lysis, that is lysis of PNH cells and of normal red cells treated in vitro with the sulphydryl compound 2-aminoethylisothiouronium bromide (AET). The conclusions, almost identical for PNH and AET lysis experiments, suggest that for the laboratory diagnosis of PNH: (1) it is advisable to use both tests in parallel; (2) sera to be used in the two tests should be selected; (3) for this selection AET cells can be employed when PNH cells are not available.

1. Durch Cysteamin (100–500 mg/kg) und AET (100–250 mg/kg) wird der Gesamt-O2-Verbrauch der Maus, besonders in der ersten 1/4 Std nach der i.p.-Injektion, herabgesetzt. 2. Zu spateren Zeitpunkten kommt es nach hoheren Dosen von Cysteamin zu einer (teilweise signifikanten) Erhohung des Gesamtstoffwechsels, die im Zusammenhang mit der starken motorischen Unruhe der Versuchstiere steht. 3. Auch bei AET geht die Verminderung des O2-Verbrauchs im weiteren Versuchsverlauf wieder zuruck, bleibt aber zu allen Zeitpunkten linear dosisabhangig. 4. Beide Stoffevermindern dosisabhangigdie Korpertemperatur. 5. Die Bedeutung dieser Reaktionen fur den Mechanismus des Strahlenschutzes durch Cysteamin und AET wird erortert.

SummaryAdministration of two radio-protectors (AET and serotonine) and two monoaminooxydase inhibitors (marsilid and catron) leads to an increase in excretion of taurine and creatine rats. This increase is similar to that produced by x-irradiation. Radioprotectors and MAO inhibitors given together with x-irradiation produce a more marked response than either treatment alone, but this response is less than the sum of the individual effects. An attempt to explain this observation has been made.

Ten kinds of N-substituted-2-(2-aminoethyl)thiopseudoureas (AETs) were prepared. 1'-Phenyl-AET (VI) gave 2-aminothiazoline derivative (XXIII) with one equivalent of alkali, while other AETs having at least one hydrogen atom at the amino nitrogen underwent intramolecular rearrangement to give MEGs. GEDs were prepared from these MEGs by mild oxidation. The NMR and IR spectra of these compounds were also discussed.

A study was made of the effect of S, 2-aminoethylisothiuronium bromide hydrobromide (AET) on the changes in sodium and potassium concentrations in the walls and contents of the gastrointestinal tracts of mice exposed to 1500 r. Mice were given AET and then irradiated. At intervals thereafter, portions of the gastrointestinal tract and its contents were analyzed for sodium and potassiura in a flame spectrophotometer. In mice given AET before exposure to 1500 r, the following radiation-induced abnormalities were completely or partially corrected: decrease in potassium and increase in sodium in the wall of the small intestine; decrease in potassium in the colon wall; and increase in sodium and potassium in the contents of the stomach, small intestine and colon. Extracts from the walls of the small intestines of AET-treated or nontreated, irradiated mice were analyzed chemically for esterase activity. In AET-treated, irradiated mice, complete recovery of esterase activity was observed by day 7 after 900 r; and partial recovery occurred after 1500 r. Since AET reduces radiation damage and thereby allows recovery, the beneficongestion; in irradiated (400 r) mice, it was slightly shrunk, and considerably shrurk after combined irradiation. It was concluded that the effect of internal (topical) irradiation onmore » tumor cells and on blood vessels was considerably increased by combination with external (systemic) irradiation or vice versa. (auth)« less

The uptake of Cr51 chromate by thymocytes in vitro after whole body X-irradiation can be used as a sensitive quantitative criterion not only for the evaluation of early radiation damage to these cells but also as a measure of later regeneration. The development of the radiation lesion is characterized by a reduction in the in vitro uptake of Cr51 and the later regeneration of new cells by an increase in Cr51 uptake which is probably due to increased uptake of Cr51 by the young newly formed cells in the damaged tissue which is proliferating in an attempt to repair the damage. The return of the Cr51 uptake to normal is an indication of the time required for the cell population (ratio of young to older cells) to return to normal. By this technique the effect of different doses of X-irradiation on the regeneration of thymocytes has been demonstrated. Treatment with AET before whole body X-irradiation (400 r) indicated that less regeneration was necessary but the recovery time remained unchanged. Age differences produced a change in the extent of repair or regeneration but no change in recovery time.Spermatozoa showed evidence of early damage after whole body X-irradiation. This damage increased with time with no evidence of increased regeneration or repair.

Pretreatment by intraperitoneal administration of WR 2721 at 400 mg/kg body weight in mice receiving 4.0 Gy X rays was found to have an appreciable antimutagenic effect with regard to reciprocal translocation induction in spermatogonia. The effectiveness of the product tested proved superior to that of a radioprotective mixture of ATP-AET-serotonin given at optimal dose ratio--360, 24, and 8 mg/kg body weight, respectively. The RF (Reduction Factor) was 2.4 for WR 2721 and 1.8 for the mixture. The effect observed indicated WR 2721 to have potential capabilities for reducing the genetic risk of radiation in male individuals.

A method for the simultaneous enumeration of human lymphocyte subpopulations was developed by mixing lymphocytes, sheep red blood cells and immunobeads. Thymus-dependent lymphocytes (T cells) are detected by rosette formation with AET-treated sheep blood cells, and thymus-independent lymphocytes (B cells) are identified by rosette formation with polyacrylamide gel coated with antibody specific to both light chains (Χ and Λ) of immunoglobulin. The major advantage of this technique is that it is simple, convenient and reproducible. This method also detects lymphocytes possessing both T and B cell markers (double-marker lymphocytes). Three different types of rosettes are distinguishable under light-microscopic observation, and this method may be valuable in clinical use.

Kell null red blood cell samples can be prepared using 2-aminoethylisothiouronium bromide (AET). This article describes a modification whereby only three drops of a 5% red blood cell suspension may be AET treated. This procedure has been used routinely in the authors' laboratory for more than a year. One patient's serum contained anti-Kpb plus anti-C and anti-D. Tests with panel cells pretreated with AET made it possible to identify underlying Rh antibodies without using a panel of genetic Kpb negative red blood cells. Of 24 red blood cell eluates from patient sample with warm autoantibodies, one had specificity within the Kell blood group system. This small volume AET-treatment method is a quick screen for the differentiation of a Kell-related specificity from a non-Kell specificity of both warm autoantibodies and alloantibodies to high-incidence antigens.

The chemical radioprotective agent, AET (S, 2b-Aminoethylisothiuronium·Br·HBr), becomes MEG (2-Mercaptoethylguanidine) (Fig. 1) at pH 7 (1). Since these preparations chemically resemble antithyroid compounds, it is important to determine whether some of their protective action may be mediated through the thyroid gland. This is a report on the effect of AET and MEG on radioactive iodine uptake. Materials and Methods: One hundred and sixty-seven Sprague-Dawley male rats weighing 90 to 190 gm. were fed a Remington diet for five days prior to the experiments. Freshly prepared AET or MEG was injected intraperitoneally, followed in thirty minutes by an intraperitoneal injection of 0.5 or 1.0 microcurie of carrier-free 1131 as iodide. At two, four, six, and twenty-four hours after the injection of AET or MEG the animals were sacrificed and the thyroid glands were removed and individually counted in a well-type scintillation counter to measure radioactive iodine uptake. The effect of dose variation was studied wi...

Whole-body gamma irradiation in the rat produced significant whole-blood cholinesterase depression on the tenth day at a dosage level of 75 r. The levels tested when plotted and extrapolared indicated threshold changes in cholinesterase activity would be in the vicinity of 20 to 30 r. AET alone, while producing some mild cholinesterase depression, failed to protect whole-blood cholinesterase activity from the effects of gamma irradiation at the levels of agent and irradiation tested. (auth)

Neither cysteine nor AET increased the selectivity of action of merophan in rats bearing the Walker tumour, while in mice bearing a plasma cell tumour, AET enhanced the selectivity of action as measured by therapeutic index. Time of administration of the thiols was important in determining the relative protective action on the host and tumour, and was well correlated with time curves of SH concentration in the tissues.

Human lymphocytes will rosette with human red blood cells under certain conditions (H rosettes). The work presented in this paper documents the following: (1) a reproducible short-term assay for the detection of H rosettes in proportions similar to those reported recently in the literature (25-30%); (2) technical improvements on the basic assay system demonstrating that, in fact, 40-65% of human lymphocytes form H rosettes; (3) the fact that, in normal donors, auto and allo H rosettes are formed by identical lymphocyte subpopulations; (4) that H rosettes are formed independently of the ABH, Rh and Thomsen-Freidenreich (TF) red-cell antigens on the indicator red cells; and (5) that H rosette-forming cells consist almost entirely of T lymphocytes having high-affinity receptors for sheep erythrocytes. The large difference in size between sheep and human RBC made it possible to do double rosette assays in which high- and low-affinity E-rosette-forming T cells could be visualized on the same slide. As with T lymphocytes in general, a large proportion of HRFC was found to have Fc-IgM receptors while a smaller proportion has Fc-IgG receptors. Studies done on a small group of leukemic patients supported the T-cell nature of the H rosette-forming cell.

C57BL++ mice were either whole body X-irradiated with a dose of 200 R or, 15 minutes before X-irradiation injected with AET, MEA, or 5-HT, in a dose of 40 mg/kg of body weight, on the first day of gestation. Uterine contents were examined on the nineteenth day of pregnancy. The number of corpora lutea was assumed as 100% and the percentage values of live and dead foetuses, resorptions, and non-implanted embryos were calculated. The percentage ratio of females with live foetuses in the uterus, in relation to the total number of those with a vaginal plug was also determined. X-irradiation of pregnant mice influenced the embryonic survival. As compared with controls, in only X-irradiated mice a lower percentage value of live foetuses and higher percentage values of non-implanted embryos and resorptions were found. One dead foetus was only observed in X-irradiated females. Percentage value of X-irradiated females with live foetuses was lower than that of control ones. High mortality of embryos occurred more often before than after the implantation of blastocysts. The percentage value of non-implanted embryos was higher than that of resorptions. AET, MEA, and 5-HT when injected to mice before their X-irradiation acted as radioprotectors. The strongest radioprotective effect was obtained following AET administration, intermediate after 5-HT treatment and the weakest one when MEA was injected.

Protection to mice bone marrow stem cells has been noted as early as two days after whole body gamma ray exposure by prior treatment with combination of hydroxytryptophan (HT) and one of the two thiol drugs viz., aminoethylisothiuronium bromide hydrobromide (AET) (20 mg/kg body weight) and B-mercaptopropionylglycine (MPG). The levels of protection to bone marrow stem cells thus obtained have been compared to that obtained by treating with the optimum radioprotecting dose of AET (200 mg/kg body weight). The study reports the bone marrow stem cells status after two days of 3 Gy, 5 Gy and 10 Gy whole body gamma irradiation in relation to the mentioned radioprotecting treatments as studied by spleen colony forming method.

Comparison of chemical protection against electromagnetic radiations (X- and gamma-rays) and high-energy proton radiations give evidence that the mechanism of antiradiation effects of radioprotectors and other biological protectors against different radiations is identical. On the basis of the data published in the literature it has been shown that the degree of radiation protection of animals and other biological objects in comparable doses differs insignificantly during exposures to proton and standard irradiations.

A study was made of the radioprotective effect of Adeturon, a protective agent obtained in Bulgaria, on mice with Luis lung tumors exposed to fractionated radiation. The effect of the radioprotector on a radiation-induced injury to normal tissue was estimated by the number of leucocytes in the peripheral blood and its count, cellularity of bone marrow and spleen and the mass of the latter, and by the number of exogenous and endogenous CFUs. A pronounced radioprotective effect of Adeturon was implemented through maintaining or normalizing the indices under study impaired by tumor inoculation or irradiation.

Adult Swiss male mice were injected intraperitoneally with 2-aminoethylesothiouronium bromide hydrobromide (AET) or cysteamine hydrochloride (MEA) in a dose of 400 mg/kg body weight. In the thirtieth, sixtieth or ninetieth minute after the injection, the animals were killed and the deoxyribonuclein acid content in 100 mg of fresh tissue of testes, spleen and liver, was measured. DNA was extracted from the organs by means of Burton's method, which is based on the estimation of deoxiribose content in the colour reaction with diphenylamine. The injection of AET and MEA did not distinctly influence the DNA content in the organs of mice. Statistically significant differences among the groups of mice were not observed compared to the controls, in mice treated with the compound, a decreasing tendency in the quantity of the DNA in the organs was found only.

The authors studied the influence of the serum obtained at various periods after the administration of interferon inductors (New castle disease virus, amino ethylisothiouronium, E. coli endotoxin) on the rate of rejection of the skin or cell transplant of mice C3H and CBA, and also CC57Br. The allogenous skin transplant perished more rapidly; there was also an acceleration of elimination of allogenous lymphoid cells, suppression of colony formation by the cells of allogenous bone marrow in the spleen of the irradiated recipient in administration of the serum obtained at the period of maximal content of interferon induced by the Newcastle disease virus and by amino ethylisothiouronium. The cytotoxic activity of lymphocytes of mice CC57Br against the allogenous target cells rose in the presence of these sera. The serum containing interferon induced with E. coli endotoxin failed to influence the rate of the allotransplant rejection and did not increase the cytotoxic activity of lymphocytes.

The individual effects of desferrioxamine B (DFOA), Na3Ca diethylenetriaminepentaacetic acid (DTPA), Na-salicylate, DL-penicillamine, and 2-aminoethylisothiouronium bromide hydrobromide, as well as the effect of mixed-ligand treatment on the retention and elimination of 95Nb in mice have been examined. It was found that 95Nb could easily be mobilized by a single dose of DFOA, but the best result was obtained with the DFOA and DTPA combination. Mixed-ligand treatment did not change the deposition characteristics and translocation kinetics of 95Nb.

The ability to form rosettes with rabbit red blood cells (RRBC) has been shown to be characteristic of T but not B cells from guinea pigs. In an attempt to devise an assay system to measure the guinea pig equivalent of human “active” T cells, we have investigated the effects of various conditions on RRBC binding by guinea pig lymphocytes, including incubation time, RRBC: lymphocyte ratio, presence or absence of guinea pig serum or fetal calf serum in the incubation medium, and pretreatment of RRBC with neuraminidase or 2-aminoethylisothiouronium bromide (AET). Without incubation and at a 100:1 ratio of RRBC to guinea pig lymphocytes, about 35% of guinea pig peripheral blood lymphocytes bound RRBC, similar to the number of “active” T cells in human peripheral blood as measured by rosette formation with sheep red blood cells. Cold incubation increased the number of rosetting cells to over 80%, presumably the total number of T cells. A relative decrease in the number of RRBC diminished rosetting only at ratios of 10:1 or less. Pretreatment of RRBC with neuraminidase slighily increased, whereas AET pretreatment drastically reduced the number of rosettes. Increasing concentrations of guinea pig serum in the medium up to 100% slightly inhibited rosetting. These results suggest the presence of two T-cell populations in guinea pig peripheral blood, equivalent to the human “active” and “total” rosette-forming T-cell subpopulations.

Experiments were carried out to investigate the possibility of providing chemical protection to blood forming organs and increasing animal survival rates in lethally irradiated H mice and Wistar rats. A 300 mg/kg dose of the radioprotective agent was injected intraperitoneally 15-30 min prior to irradiation with 8.0 Gy gamma rays. Recorded were 30-day survival rates and the state of hemopoiesis on days 3 and 10 postradiation as judged by spleen weight and total counts of spleno- and myelokaryocytes. At 8.0 Gy exposure was observed to cause severe spleen and bone-marrow hypoplasia on day 3 postradiation. Adeturone pretreatment provided slight protection to rat spleen and mouse bone marrow; by day 10, however, both animal species exhibited a vigorous proliferative response of nucleated cells in the bone marrow, which resulted in 75% survival rate among animals exposed to a lethal radiation dose.

Change in electrophoretic mobility (EM) of erythrocytes was studied 6 hours after rats were exposed to a dose range (0.5-4 Gy) of high-energy protons (9 GeV/nucleon) or gamma rays (0.660 MeV), with or without adeturone pretreatment (300 mg/kg body weight). With either of the two radiation types used, EM of the cells was observed to undergo significant dose-related decline. As indicated by our findings, adeturone pretreatment failed to contribute to maintenance of normal erythrocyte surface charge in the case of proton irradiation, proving, nevertheless, effective against gamma-ray exposure at all dose levels used.

180 patients with neurological or infectious diseases and 90 normal controls were examined for blood T lymphocyte percentage by the standard method using rosette formation with untreated sheep erythrocytes (E) and a technique using 2-amino-ethyl-thio-isouronium bromide hydrobromide (AET)-treated E, with fetal calf serum (FCS) in the medium. Patients with acute meningitis had a decrease and those with infections mononucleosis had an increase in T lymphocyte percentage as measured by both assays. However, patients with active MS and with cerebral tumours had a decrease in T cell percentage by the E but not by the EAET technique. The T lymphocyte percentages of the other 4 patient groups did not differ significantly from those of the controls, regardless of the technique used. In certain diseases, the use or not of AET-treated indicator cells may thus influence the results of the rosette test.

Effect of whole body gamma irradiation (1200 r) on spleen lipid metabolism of male and female rats 24 hrs and 48 hrs after irradiation and the effect of radioprotective chemicals vis. AET, serotonin, their mixture and cystamine on radiation induced changes in spleen lipid metabolism has been studied. In male rats both 24 and 48 hrs after irradiation a significant increase in spleen total lipids, cholesterol, phospholipids, phosphatidylethanolamine and phosphatidylcholine was observed. Administration of AET before irradiation prevented the changes in spleen total lipids and cholesterol but not in phospholipids, which was prevented by prior administration of both serotonin and the mixture of serotonin and AET. In female rats 24 hrs after irradiation only spleen total lipids showed an increase which was prevented by prior administration of cystamine. In male rats, 24 hrs after irradiation the incorporation of NaH2 32PO4 (counts/min/ug PLP and counts/min/g spleen) into spleen total phospholipids, phosphatidylcholine and phosphatidylethanolamine was reduced and this was corrected by prior administration of AET. Serotonin and the mixture of serotonin + AET did not protect the specific activity of phosphatidy choline. In female rats irradiation increased the incorporation of NaH2 32PO4 into phosphatidylcholine, which was not prevented by prior administration of cystamine. The fatty acid composition of spleen lipid of female rats was profoundly altered 24 hrs after irradiation. Palmitic acid and oleic acid showed an increase whereas arachidonic and fatty acid above arachidonic acid showed an decrease, which were corrected by administration of cystamine before irradiation.