286 results on '"Lawrence Grossman"'
Search Results
102. Chemical compositions of siderophile element-rich opaque assemblages in an Allende inclusion
- Author
-
Lawrence Grossman, Paul J. Sylvester, Brian Ward, and Ian D. Hutcheon
- Subjects
Allende meteorite ,Opacity ,Meteorite ,Geochemistry and Petrology ,Chondrite ,Mineralogy ,Inclusion (mineral) ,Formation and evolution of the Solar System ,Chemical composition ,Refractory (planetary science) ,Geology - Abstract
Chemical compositions of ten opaque assemblages, or Fremdlinge, from an Allende Type B Ca-,Al-rich coarse-grained inclusion were determined. Attempts to model the abundances of refractory siderophiles assuming condensation from the solar nebula into a single phase failed to match the observed combination of subchondritic Re/Os and Ir/Pt ratios. However, virtually all refractory siderophile fractionations in these Fremdlinge could be matched by a different model, in which all metals condensed into three separate alloys according to their crystal structures.
- Published
- 1990
103. Chemical compositions of refractory inclusions from the Vigarano and Leoville carbonaceous chondrites
- Author
-
Lawrence Grossman, Xue-Ying Mao, Brian Ward, and Glenn J. MacPherson
- Subjects
Allende meteorite ,Refractory ,Meteorite ,Geochemistry and Petrology ,Chondrite ,Mineralogy ,Inclusion (mineral) ,Formation and evolution of the Solar System ,Volatiles ,Chemical composition ,Geology - Abstract
The contents of the major and the trace elements of three refractory inclusions from Leoville and two hibonite-rich refractory inclusions and a dark clast from Vigarano were investigated using INAA technique, and the results were compared with results reported for an Allende inclusion. It was found that two out of the three refractory inclusions from Leoville and both inclusions from Vigarano have lower Na and Au contents than the coarse-grained inclusion from Allende. It is shown that the concentrations of all volatile elements in refractory inclusions in the Leoville and Vigarano meteorites tend to be either below or at the low end of their concentration ranges in Allende coarse-grained inclusions. This is considered to be due to the fact that the former were altered in parts of the solar nebula where grain-bias separation processes removed the inclusions from chemical communication with the gas at a higher temperature or after a shorter time than for the inclusions from Allende.
- Published
- 1990
104. THE UvrABC ENDONUCLEASE OFEscherichia coli
- Author
-
Anthony T. Yeung and Lawrence Grossman
- Subjects
chemistry.chemical_classification ,biology ,General Medicine ,medicine.disease_cause ,biology.organism_classification ,Biochemistry ,Enterobacteriaceae ,Microbiology ,Endonuclease ,chemistry.chemical_compound ,Enzyme ,chemistry ,medicine ,biology.protein ,Physical and Theoretical Chemistry ,Nuclear protein ,Escherichia coli ,Bacteria ,DNA ,UvrABC endonuclease - Published
- 1990
105. The role of Escherichia coli UvrB in nucleotide excision repair
- Author
-
Lawrence Grossman and T W Seeley
- Subjects
chemistry.chemical_classification ,biology ,DNA repair ,ATPase ,Mutant ,Cell Biology ,Gene mutation ,Biochemistry ,Molecular biology ,chemistry.chemical_compound ,chemistry ,ATP hydrolysis ,biology.protein ,bacteria ,Nucleotide ,Molecular Biology ,DNA ,Nucleotide excision repair - Abstract
The role of UvrB in determining the nucleotide dependence of Escherichia coli excision repair has been investigated. The mutation of lysine 45 in the ATPase motif of UvrB to alanine leads to an acute defect in ATP hydrolysis and failure to support incision of UV-damaged DNA. This ATP hydrolysis activity is not required for interaction of UvrB with UvrA in solution, or for formation of a damage-independent nucleoprotein complex in the presence of UvrA and nucleotide. This UvrB mutant fails, however, to support damage-specific nucleoprotein complex formation, and does not participate in a UvrA-UvrB-dependent helicase-like activity. We conclude from these results that mutation at lysine 45 in the ATPase motif of UvrB specifically inhibits a key step in nucleotide excision repair involving the UvrB ATPase-dependent translocation of nucleoprotein complexes from undamaged to damaged DNA sites.
- Published
- 1990
106. Complementation of the xeroderma pigmentosum DNA repair synthesis defect withEscherichia coliUvrABC proteins in a cell-free system
- Author
-
Richard D. Wood, Johan Hansson, Lawrence Grossman, and Tomas Lindahl
- Subjects
congenital, hereditary, and neonatal diseases and abnormalities ,Xeroderma pigmentosum ,DNA Repair ,Ultraviolet Rays ,DNA damage ,DNA repair ,Biology ,Microbiology ,chemistry.chemical_compound ,Plasmid ,Escherichia coli ,Genetics ,medicine ,Ultraviolet light ,Humans ,skin and connective tissue diseases ,Xeroderma Pigmentosum ,Endodeoxyribonucleases ,Cell-Free System ,integumentary system ,Escherichia coli Proteins ,Genetic Complementation Test ,nutritional and metabolic diseases ,medicine.disease ,Molecular biology ,Complementation ,chemistry ,Cisplatin ,Dysplastic Nevus Syndrome ,DNA ,DNA Damage ,Plasmids ,Nucleotide excision repair - Abstract
A newly developed cell-free system was used to study DNA repair synthesis carried out by extracts from human cell lines in vitro. Extracts from a normal human lymphoid cell line and from cell lines established from individuals with hereditary dysplastic nevus syndrome perform damage-dependent repair synthesis in plasmid DNA treated with cis- or trans-diamminedichloro-platinum(II) or irradiated with ultraviolet light. Cell extracts of xeroderma pigmentosum origin (complementation groups A, C, D, and G) are deficient in DNA repair synthesis. When damaged plasmid DNA was pretreated with purified Escherichia coli UvrABC proteins, xeroderma pigmentosum cell extracts were able to carry out DNA repair synthesis. The ability of E. coli UvrABC proteins to complement xeroderma pigmentosum cell extracts indicates that the extracts are deficient in incision, but can carry out later steps of repair. Thus the in vitro system provides results that are in agreement with the incision defect found from studies of xeroderma pigmentosum cells.
- Published
- 1990
107. A stellar origin for the short-lived nuclides in the early Solar System
- Author
-
Roy S. Lewis, J. N. Goswami, Andrew M. Davis, S. Sahijpal, and Lawrence Grossman
- Subjects
Physics ,Solar System ,Multidisciplinary ,Stable nuclide ,Isotope ,Nuclide ,Primordial nuclide ,Formation and evolution of the Solar System ,p-process ,Accretion (astrophysics) ,Astrobiology - Abstract
Primitive meteorites contain isotopes that are the decay products of short-lived nuclides in the early Solar System1,2. The relative abundances of these isotopes provide a means to determine timescales for the formation and accretion of primitive Solar System objects, the abundances of the parent nuclides being fixed when these objects solidified. The abundances can also be used to investigate the source of the nuclides (such as 41Ca, 26Al, 60Fe, 53Mn and 107Pd), although this is an area of controversy. The nuclides could have originated from a single stellar object2,3,4,5,6, such as a nearby red-giant or a supernova. But observations of enhanced ion fluxes in a molecular cloud7 have led to other models8,9,10 in which these nuclides are formed by energetic particle irradiation of gas and dust in the protosolar molecular cloud; alternatively, irradiation by energetic particles from the active early Sun may have occurred within the solar nebula itself11,12,13,14,15,16,17,18. Here we show that there is a correlation between the initial abundances of 41Ca and 26Al in samples of primitive meteorite (as inferred from their respective decay products, 41K and 26Mg), implying a common origin for the short-lived nuclides. We can therefore rule out the mechanisms based onenergetic particle irradiation, as they cannot produce simultaneously the inferred initial abundances of both nuclides. If, as our results suggest, a single stellar source is responsible for generating these nuclides, we can constrain to less than one million years the timescale for the collapse of the protosolar cloud to form the Sun.
- Published
- 1998
108. Phosphodiesterases Involved in DNA Repair
- Author
-
Bernard Weiss and Lawrence Grossman
- Subjects
Biochemistry ,DNA repair ,Chemistry ,Phosphodiesterase ,Nucleotide excision repair - Published
- 2006
109. Mineralogy and Petrology of Comet 81P/Wild 2 Nucleus Samples
- Author
-
Frank J. Stadermann, Matthew J. Genge, Anders Meibom, David J. Joswiak, D. A. Papanastassiou, Nick Teslich, Lindsay P. Keller, Kyoko Okudaira, Sean Brennan, Thomas H. See, Jean Susini, M. K. Weisberg, Matthieu Gounelle, Frans J. M. Rietmeijer, Keiko Nakamura-Messenger, Zu Rong Dai, J. Warren, Donald E. Brownlee, Loan Le, Kazushige Tomeoka, Pierre Bleuet, Steven B. Simon, Stewart Fallon, Alice Toppani, Damien Jacob, Mitra L. Taheri, John P. Bradley, Denton S. Ebel, Adrian J. Brearley, Laurence Lemelle, Thomas J. Zega, Jeffrey N. Grossman, Philippe Gillet, Falko Langenhorst, Takashi Mikouchi, Akira Tsuchiyama, John Bridges, Michael E. Zolensky, François Robert, Hope A. Ishii, Alexander N. Krot, Anna L. Butterworth, Giles A. Graham, Rhonda M. Stroud, Michael A. Velbel, Christopher J. Snead, Ron K. Bastien, Miaofang Chi, Antonio Lanzirotti, Graciela Matrajt, Benton C. Clark, Murielle C. Perronnet, Thomas Stephan, Kazumasa Ohsumi, Naotaka Tomioka, Patrick Cordier, Iris Weber, Anton T. Kearsley, George J. Flynn, Matthew A. Marcus, Tomoki Nakamura, Smail Mostefaoui, Hugues Leroux, William Rao, Ichiro Ohnishi, Sue Wirick, Ralph P. Harvey, Peter Tsou, T. Ferroir, Hajime Yano, Kenji Hagiya, Phil Bland, Lawrence Grossman, Andrew J. Westphal, Alexandre Simionovici, European Synchrotron Radiation Facility (ESRF), Laboratoire de Sciences de la Terre (LST), Centre National de la Recherche Scientifique (CNRS)-Institut national des sciences de l'Univers (INSU - CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-École normale supérieure - Lyon (ENS Lyon), Institut d'Informatique et de Mathématiques Appliquées de Grenoble (IMAG), Université Joseph Fourier - Grenoble 1 (UJF)-Institut National Polytechnique de Grenoble (INPG)-Centre National de la Recherche Scientifique (CNRS), Laboratoire Environnement et Minéralurgie (LEM), Institut National Polytechnique de Lorraine (INPL)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Modélisation des Transferts dans l'Environnement (LMTE), Service Mesures et modélisation des Transferts et des Accidents graves (SMTA), Département Technologie Nucléaire (DTN), CEA-Direction des Energies (ex-Direction de l'Energie Nucléaire) (CEA-DES (ex-DEN)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-CEA-Direction des Energies (ex-Direction de l'Energie Nucléaire) (CEA-DES (ex-DEN)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Département Technologie Nucléaire (DTN), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Advanced Light Source [LBNL Berkeley] (ALS), Lawrence Berkeley National Laboratory [Berkeley] (LBNL), Laboratoire de structures et propriétés de l'état solide - UMR 8008 (LSPES), Université de Lille, Sciences et Technologies-Centre National de la Recherche Scientifique (CNRS), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Université de Lyon-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS)
- Subjects
Multidisciplinary ,Olivine ,x-ray fluorescence ,Chemistry ,Comet ,Sulfur XANES ,Mineralogy ,Pyroxene ,engineering.material ,010502 geochemistry & geophysics ,Protoplanetary disk ,Stardust ,01 natural sciences ,Astrobiology ,Carbonaceous chondrite ,Silicate minerals ,0103 physical sciences ,engineering ,Formation and evolution of the Solar System ,010303 astronomy & astrophysics ,Refractory (planetary science) ,0105 earth and related environmental sciences ,[SDU.STU.MI]Sciences of the Universe [physics]/Earth Sciences/Mineralogy - Abstract
著者人数: 75名, 資料番号: SA1003700000
- Published
- 2006
110. Jewish religious denominations
- Author
-
Dana Evan Kaplan and Lawrence Grossman
- Subjects
Judaism ,Political science ,Religious studies - Published
- 2005
111. DNA repair and breast carcinoma susceptibility in women
- Author
-
B S Abigail Ruiz, Juan M. Ramos, D B S Ivette Lopez, Lawrence Grossman, Jaime Matta, and Rivka Colen
- Subjects
Oncology ,Adult ,Cancer Research ,medicine.medical_specialty ,DNA Repair ,Mammary gland ,Breast Neoplasms ,medicine.disease_cause ,Risk Factors ,Internal medicine ,Surveys and Questionnaires ,parasitic diseases ,Carcinoma ,medicine ,Humans ,Lymphocytes ,Risk factor ,Luciferases ,Aged ,Gynecology ,business.industry ,Carcinoma, Ductal, Breast ,Case-control study ,Cancer ,Odds ratio ,Middle Aged ,medicine.disease ,medicine.anatomical_structure ,Logistic Models ,Case-Control Studies ,Female ,business ,Carcinogenesis ,Breast carcinoma - Abstract
BACKGROUND Breast carcinoma is the most common cancer and the second leading cause of cancer-related deaths among women. The disease represents approximately 31% of all cancers in Puerto Rican women. Several DNA repair pathways are involved in preventing carcinogenesis. The current study evaluated the hypothesis that a reduced DNA repair capacity (DRC) is a susceptibility factor for breast carcinoma. METHODS A retrospective case–control clinical study was performed to compare age-matched DRC in 33 women with histopathologically confirmed breast carcinoma (cases) and 47 cancer-free women (controls). DRC was measured using a host cell reactivation assay with a luciferase reporter gene and then transfected into human peripheral lymphocytes. A questionnaire was used to solicit breast carcinoma risk factors. RESULTS Women with breast carcinoma had a mean DRC of 5.6% ± 0.5 standard error of the mean (SEM). Cancer cases had a 36% reduction (P < 0.001) in DRC when compared with the control group (DRC = 8.7% ± 0.7 SEM). Younger participants with breast carcinoma were found to have a more significant reduction in DRC when compared with age-matched controls. Family (odds ratio [OR] = 4.1), maternal lineage (OR = 5.5), and maternal (OR = 12.4) history of breast carcinoma were found to be the only statistically significant (P < 0.05) risk factors associated with the disease. CONCLUSIONS The findings supported the hypothesis that a low DRC is a susceptibility factor for breast carcinoma. A 1% decrease in DRC corresponded to a 22% increase in breast carcinoma risk. To the authors' knowledge, the current study was the first to directly determine the DRC of women with breast carcinoma. Because DRC is an independent risk factor for breast carcinoma, the DRC of women may be a useful marker in predicting susceptibility. Cancer 2004;100:1352–7. © 2004 American Cancer Society.
- Published
- 2004
112. Deficient nucleotide excision repair capacity enhances human prostate cancer risk
- Author
-
Kurt Lohman, Jennifer J. Hu, Lawrence Grossman, David L. McCullough, M. Craig Hall, L. Douglas Case, and Mohammad Hedayati
- Subjects
Male ,Cancer Research ,medicine.medical_specialty ,DNA Repair ,Gastroenterology ,Prostate cancer ,Risk Factors ,Internal medicine ,medicine ,Humans ,Family history ,Risk factor ,Aged ,Gynecology ,business.industry ,Cancer ,Prostatic Neoplasms ,Odds ratio ,Middle Aged ,medicine.disease ,Confidence interval ,Oncology ,Quartile ,Case-Control Studies ,Etiology ,business - Abstract
Prostate cancer (CaP) is the most commonly diagnosed non-skin cancer and the second leading cause of cancer death in American men. The etiology of CaP is not fully understood. Because most of the DNA adducts generated by some CaP-related carcinogens, including polycyclic aromatic hydrocarbons, heterocyclic amines, and pesticides, are removed by the nucleotide excision repair (NER) pathway, we pilot tested the hypothesis that CaP is associated with deficient NER capacity (NERC), measured by a plasmid-based host reactivation assay. Using cryopreserved lymphocytes collected in an ongoing, clinic-based case-control study, our results showed that the mean NERC was significantly lower (P = 0.03) in 140 cases (mean ± SD, 8.06 ± 5.17) than in 96 controls (9.64 ± 5.49). There was a significant association between below-median NERC and CaP risk: odds ratio (OR), 2.14; 95% confidence interval (CI), 1.19–3.86, after adjustment for age, race/ethnicity, smoking history, benign prostatic hyperplasia, and family history. This association was stronger in younger (
- Published
- 2004
113. Nucleotide Excision Repair, Bacterial: The UvrABCD System
- Author
-
Bennett Van Houten and Lawrence Grossman
- Published
- 2004
114. Nucleotide Excision Repair in Escherichia coli
- Author
-
Chien-liang Lin, Lawrence Grossman, and Yungchan Ahn
- Subjects
Chemistry ,medicine ,medicine.disease_cause ,Escherichia coli ,Molecular biology ,Nucleotide excision repair - Published
- 2003
115. Multiple single nucleotide polymorphisms on human chromosome 19q13.2-3 associate with risk of Basal cell carcinoma
- Author
-
Jiaoyang, Yin, Eszter, Rockenbauer, Mohammad, Hedayati, Nicklas Raun, Jacobsen, Ulla, Vogel, Lawrence, Grossman, Lars, Bolund, and Børn A, Nexø
- Subjects
Family Health ,Male ,Skin Neoplasms ,Genotype ,Molecular Sequence Data ,Exons ,Sequence Analysis, DNA ,Middle Aged ,Polymorphism, Single Nucleotide ,Introns ,Linkage Disequilibrium ,White People ,Gene Frequency ,Carcinoma, Basal Cell ,Risk Factors ,Biomarkers, Tumor ,Humans ,Female ,Genetic Predisposition to Disease ,Chromosomes, Human, Pair 19 ,Alleles - Abstract
In this paper, we present evidence that alleles of several polymorphisms in the chromosomal region 19q13.2-3, encompassing the genes RAI and XPD, are associated with occurrence of basal cell carcinoma in Caucasian Americans. The association of one of these, RAI-intron1, is sufficiently strong to make mass significance unlikely (P = 0.004, chi(2)). We interpret our combined data to indicate that a specific haplotype partly defined by the alleles of three single nucleotide polymorphisms, RAI intron1(G), RAI exon6(T), and XPD exon 6(C), is associated with a protective gene variant in a region spanning from XPD to ERCC1.
- Published
- 2002
116. Rapid genotyping of human ERCC1 exon 4 polymorphism with fluorescence analysis using fluorophore-labeled hybridization probes and a lightcycler
- Author
-
Jiaoyang, Yin, Mohammad A, Hedayati, Lawrence, Grossman, Lars, Bolund, and Bjorn A, Nexo
- Subjects
DNA-Binding Proteins ,Genotype ,Humans ,Proteins ,Fluorometry ,Exons ,Endonucleases ,Polymorphism, Single Nucleotide - Published
- 2002
117. Modulation of repair of ultraviolet damage in the host-cell reactivation assay by polymorphic XPC and XPD/ERCC2 genotypes
- Author
-
Lawrence Grossman, Yawei Qiao, Mohammad Hedayati, Harvey W. Mohrenweiser, Qingyi Wei, Sanjay Shete, Hongbing Shen, Margaret R. Spitz, and Zhaozheng Guo
- Subjects
Cancer Research ,DNA Repair ,Genotype ,DNA damage ,DNA repair ,Ultraviolet Rays ,Biology ,medicine.disease_cause ,Host-Cell Reactivation ,XRCC1 ,Neoplasms ,parasitic diseases ,medicine ,Humans ,Genetic Predisposition to Disease ,Xeroderma Pigmentosum Group D Protein ,Genetics ,Polymorphism, Genetic ,Homozygote ,DNA Helicases ,Proteins ,General Medicine ,Base excision repair ,Exons ,DNA-Binding Proteins ,Phenotype ,X-ray Repair Cross Complementing Protein 1 ,ERCC2 ,Carcinogenesis ,Nucleotide excision repair ,DNA Damage ,Transcription Factors - Abstract
DNA repair capacity (DRC) plays an important role in genetic susceptibility to cancer. Polymorphisms of a number of DNA repair genes involved in several distinct pathways have been identified. However, their effects on repair function have not been well characterized. We demonstrated previously that DRC for removal of benzo[a]pyrene diol epoxide-induced DNA damage measured by a host-cell reactivation assay was modulated by two XPD/ERCC2 polymorphisms in lung cancer. In this report, we investigated the association between the repair phenotype of ultraviolet (UV)-induced damage and genotypes of three DNA repair genes, XPC and XPD [involved in nucleotide excision repair (NER)] and XRCC1 [involved in base excision repair (BER)]. We measured DRC for removal of UV photoproducts by the host-cell reactivation assay in cryopreserved lymphocytes from 102 healthy non-Hispanic white subjects. We also typed these subjects for five polymorphisms in these three DNA repair genes (at intron 9 of XPC; exons 6, 10 and 23 of XPD and exon 10 of XRCC1). Compared with wild-type homozygotes, subjects homozygous for polymorphisms of the two NER genes consistently had suboptimal DRC. The DRC was consistently lower in subjects homozygous for XPC, XPD or both than in subjects with other genotypes, although the difference was not statistically significant for XPD variants. In contrast, the polymorphic allele of the BER gene, XRCC1, had no consistent effect on DRC. We concluded that these NER polymorphisms may modulate DRC and may be useful biomarkers for identifying individuals at risk of developing cancer.
- Published
- 2002
118. DNA repair, dysplastic nevi, and sunlight sensitivity in the development of cutaneous malignant melanoma
- Author
-
Margaret A. Tucker, Angela Cecilia Pesatori, Mohammad Hedayati, Andrea A. Baccarelli, Maria Teresa Landi, Robert E. Tarone, and Lawrence Grossman
- Subjects
Oncology ,Adult ,Male ,Cancer Research ,medicine.medical_specialty ,Skin Neoplasms ,DNA Repair ,Lymphocyte ,Risk Factors ,Internal medicine ,parasitic diseases ,medicine ,Humans ,Risk factor ,Melanoma ,Aged ,Skin ,Likelihood Functions ,business.industry ,Case-control study ,Cancer ,Odds ratio ,Middle Aged ,medicine.disease ,Surgery ,medicine.anatomical_structure ,Relative risk ,Case-Control Studies ,Dysplastic nevus ,Sunlight ,Female ,business ,Dysplastic Nevus Syndrome - Abstract
Background: Exposure to UV radiation is associated with cutaneous malignant melanoma (CMM). In mammalian cells, UV radiation induces DNA damage that can be repaired by the nucleotide excision repair system. We designed this case–control study to determine whether DNA repair capacity (DRC) is associated with the risk of CMM and to identify risk factors that may interact biologically with DRC in the development of melanoma. Methods: Global DRC was measured in lymphocytes with the host-cell reactivation assay. Data were analyzed by use of multiple regression models. All statistical tests were two-sided. Results: DRC could be determined for 132 case patients with incident melanoma and for 145 age- and sex-matched control subjects. No statistically significant association between melanoma risk and DRC by itself was found (odds ratio [OR] = 1.0; 95% confidence interval [CI] = 0.6 to 1.7, adjusted for age, sex, lymphocyte viability, and sample storage time). DRC, however, strongly influenced CMM risk in individuals with a low tanning ability or dysplastic nevi. Individuals with a low tanning ability and a low DRC had a higher risk for CMM (OR = 8.6; 95% CI = 2.7 to 27.5) than individuals with a higher tanning ability and a high DRC. Likewise, individuals with dysplastic nevi and a low DRC had a higher relative risk (OR = 6.7; 95% CI = 2.4 to 18.6) than those lacking dysplastic nevi and having a high DRC. Subjects with dysplastic nevi and a high DRC had an intermediate risk. A likelihood-ratio test gave statistically significant interactions between DRC and tanning response (P = .001) and between DRC and dysplastic nevus status (P = .04), which were independently associated with CMM risk. Conclusions: DRC may modify the risk for melanoma in the presence of other strong risk factors, such as a low tanning ability and the presence of dysplastic nevi. The occurrence of melanoma in subjects without these risk factors appears to be independent of DRC. [J Natl Cancer Inst 2002;94:94–101]
- Published
- 2002
119. Association of chromosome 19q13.2-3 haplotypes with basal cell carcinoma: Tentative delineation of an involved region using data for single nucleotide polymorphisms in two cohorts
- Author
-
Bjørn A. Nexø, Eszter Rockenbauer, Nicklas Raun Jacobsen, Lars Bolund, Lawrence Grossman, Zuzanna Bukowy, Ulla Vogel, Mohammad Hedayati, Mette H. Bendixen, and Jiaoyang Yin
- Subjects
Adult ,Cancer Research ,Skin Neoplasms ,Genotype ,Single-nucleotide polymorphism ,Biology ,Polymorphism, Single Nucleotide ,Cohort Studies ,Exon ,hemic and lymphatic diseases ,Genetic variation ,Humans ,Gene ,Genetics ,Haplotype ,Intron ,Chromosome ,Genetic Variation ,General Medicine ,DNA ,Exons ,Sequence Analysis, DNA ,Middle Aged ,Introns ,Neoplasm Proteins ,Haplotypes ,Carcinoma, Basal Cell ,Case-Control Studies ,Chromosomes, Human, Pair 19 ,Microsatellite Repeats - Abstract
We have previously used single nucleotide polymorphisms to detect an association of basal cell carcinoma (BCC) in Caucasian Americans and Danes with the genome region 19q13.2-3, which contains several genes involved in the nucleotide excision repair of DNA. In this exploratory paper we have extended the data and used them in a chromosomal scan. The results indicate the presence of a gene variation modulating the risk of developing BSS in a submegabase region including and surrounding the gene RAI. Specifically, persons that are homozygous for the haplotype RAI intron 1(A) RAI exon 6(A) appear at increased risk for BCC. In addition, we have looked for possible synergisms between all pairs of markers. We find that a marker in GLTSCR1, presumably separated from RAI by several million bases, supplements the most significant marker in RAI in separating cases from controls, which may suggest the presence of an independent, risk-modulating variation in this second gene region.
- Published
- 2002
120. Polymorphisms of the DNA repair gene XPD: correlations with risk of basal cell carcinoma revisited
- Author
-
Bjørn A. Nexø, Lawrence Grossman, Mohammad Hedayati, Marianne Dybdahl, and Ulla Vogel
- Subjects
Silent mutation ,Adult ,Male ,Cancer Research ,Xeroderma pigmentosum ,Skin Neoplasms ,DNA Repair ,Biology ,Exon ,Genotype ,medicine ,Carcinoma ,Humans ,Basal cell carcinoma ,Genetic Predisposition to Disease ,Codon ,Alleles ,Xeroderma Pigmentosum Group D Protein ,Polymorphism, Genetic ,DNA Helicases ,Cancer ,Proteins ,General Medicine ,Exons ,Middle Aged ,medicine.disease ,DNA-Binding Proteins ,Carcinoma, Basal Cell ,Case-Control Studies ,Cancer research ,Female ,Skin cancer ,Transcription Factors - Abstract
The XPD gene product has a dual function in basal tide excision repair and basal transcription as part of the transcription and in nucleotide excision repair. We have transcription factor TFIIH (7). Mutations destroying enzymatic previously reported that two polymorphisms in the gene, function of the XPD protein is manifested clinically in comone silent mutation in codon 156 of exon 6 and one giving binations of three severe syndromes, Cockayne syndrome, rise to a Lys→Gln substitution in codon 751 of exon 23, xeroderma pigmentosum and trichotiodystrophy depending on showed signs of being associated with basal cell carcinoma the location of the mutation (8,9). In healthy individuals, the in a Scandinavian study group of psoriasis patients and non- XPD protein level may also be of importance as the mRNA psoriatics with and without basal cell carcinoma [Dybdahl, level of XPD has been shown to correlate with the DNA repair Vogel, Frentz, Wallin and Nexo (1999) Cancer Epidemiol. capacity in primary lymphoblasts (10). Biomark. Prev., 8, 77–81]. In both polymorphisms, the CC We have previously presented data to suggest that two genotype appeared to be protective against basal cell known polymorphisms in the nucleotide excision repair gene carcinoma. Here, we have genotyped an American study XPD were associated with increased risk of basal cell carcinoma group of basal cell carcinoma patients and controls without (BCC) amongst Scandinavian psoriasis patients, who through skin cancer for the two polymorphisms. In addition, we their treatment for psoriasis were exposed to very genotoxic studied an A→G polymorphism in codon 312 of exon 10, agents such as coal tar, psoralen and UV light, X-rays and which results in an Asp→Asn substitution in a conserved methotrexate. For the polymorphism in exon 23, an association region of XPD. In the whole study group, subjects carrying to BCC was suggested among psoriatics as well as nonthe AA and AC genotype in exon 6 were at 1.9-fold higher psoriatics (OR 4.3, P 0.075), whereas for the exon 6 risk of basal cell carcinoma (P 0.062, CI 0.96–3.75). If polymorphism an association was only suggested in psoriatics only subjects without a family history of non-melanoma (OR 5.3, P 0.078) (11). Subjects carrying AA genotype skin cancer were included, subjects carrying AA or AC were in both cases at higher risk of BCC. In addition, we have genotype were at 3.3-fold higher risk of basal cell carcinoma included a G→A polymorphism in codon 312 of exon 10 (P 0.007, CI 1.35–8.18). Among subjects with a family which results in an Asp→Asn substitution in an evolutionally history of non-melanoma skin cancer, subjects with an AG conserved region (12–14). or AA genotype in codon 312 of exon 10 were at 5.25-fold In the present study, we have analyzed three XPD polyincreased risk of basal cell carcinoma (P 0.027, CI morphisms in a well-described study group of American BCC 1.15–23.93). A protective effect of the CC genotype in exon patients and controls recruited at dermatological clinics (4). 23 could not be confirmed. Cases with a family history of We confirm that the XPD exon 6 CC genotype is protective skin cancer had statistically significantly different allele against basal cell carcinoma. This protective influence mainly frequencies of the polymorphisms in exon 6 and exon 10 occurs among persons without a family history of nonfrom cases without family history of non-melanoma skin melanoma skin cancer. Among subjects with a family history cancer. Our results indicate that the exon 6 A allele is a risk of non-melanoma skin cancer, the A-allele of the exon 10 factor in basal cell carcinoma. polymorphism was associated with increased risk of BCC.
- Published
- 2001
121. Age-associated changes in DNA repair and mutation rates
- Author
-
Robert E. Tarone, Satyajit Ray, Qingyi Wei, Shin-Ichi Moriwaki, Kenneth H. Kraemer, and Lawrence Grossman
- Subjects
Genetics ,Mutation rate ,Xeroderma pigmentosum ,DNA damage ,DNA repair ,medicine ,Cancer ,Biology ,Age of onset ,medicine.disease ,Carcinogenesis ,medicine.disease_cause ,Gene - Abstract
Publisher Summary Human populations typically display a range of inherent sensitivities to radiation and chemical carcinogens. Given a common carcinogenic insult, some individuals develop associated neoplasms, some may develop only an associated pre-neoplastic lesion, while others remain clinically free from all related effects of the exposure. Within specific cancer populations, age of onset, extent, and severity of neoplasia often vary among patients. Such variability in host response, in part, may be due to inherent differences among individuals to monitor and repair damaged sites induced in their genetic material by exogenous and endogenous genotoxic agents. In most cases, mutations at specific loci appear to provide the necessary signal, releasing these genes from a cryptic or quiescent state, eventuating in cancer formation. The linkage between persistent DNA damage and oncogene activity suggests that such long-lived DNA damage is a reflection of the diminished involvement of DNA repair or surveillance activities in tumorigenesis. A human model supporting such assumptions exists with the rare, cancer-prone inherited disorder xeroderma pigmentosum (XP). The life spans of organisms have been compared with the overall efficiencies of their DNA repair systems. Several human diseases with DNA repair deficiencies are associated with accelerated aging.
- Published
- 2001
122. DNA Repair as A Susceptibility Factor in Chronic Diseases in Human Populations
- Author
-
Evan R. Farmer, Lawrence Grossman, Marianne Berwick, Sugita Ray, Jennifer J. Hu, Bruce J. Trock, John Hanfelt, Genevieve M. Matanoski, George C. Roush, and Mohammad Hedyati
- Subjects
Oncology ,Premature aging ,Genetics ,medicine.medical_specialty ,education.field_of_study ,Xeroderma pigmentosum ,integumentary system ,DNA damage ,DNA repair ,business.industry ,Population ,Cancer ,medicine.disease ,Breast cancer ,Internal medicine ,medicine ,Skin cancer ,skin and connective tissue diseases ,business ,education - Abstract
Three case-control studies of DNA repair in the general population were conducted with: i. 88 primary basal cell carcinoma (BCC) cases and 135 cancer-free controls, ii 304 study subjects including 57 arsenical cancer patients and 247 noncancerous controls in Taiwan and iii 41 breast cancer patients and 73 controls. The host reactivation assay was used to measure cellular DRC capacity with cryopreserved peripheral lymphocytes from both the cases and their controls. In study i. reduced repair of UV-induced DNA damage contributed to the risk of sunlight-induced BCC. A family history of BCC is a predictor of low DNA repair. Repair of UV damaged DNA declines at a rate of about 0.6 per annum in in non-cancerous controls. In addition, reduced DNA repair is more likely seen in young BCC cases, indicating that BCC is a premature aging disease of the skin. The persistence of photochemical damage because of reduced repair, results in point mutations in the p53 gene and allelic loss of the nevoid BCC (Gorlin’s syndrome) gene located on chromosome 9q. Xeroderma pigmentosum appears to be a valid paradigm for the role of DNA repair in BCC in the general population. An extension of these studies led to conclusions from Black Foot Disease (BDF) studies that DRC by itself is not a risk factor for arsenical skin cancer, but those individuals with low DRC,are at much greater risk when exposed to high levels of arsenic in their drinking water or when they are on poor diets. DRC, therefore, appears to be a susceptibility factor in this disease. Further DRC is consistently lower in breast cancer cases than in controls and appears to be a susceptibility factor in breast cancer and DRC in lymphocytes may be employed as a biomarker for human breast cancer risk.
- Published
- 1999
123. Accessibility of epitopes on UvrB protein in intermediates generated during incision of UV-irradiated DNA by the Escherichia coli Uvr(A)BC endonuclease
- Author
-
Lawrence Grossman and Oleg I. Kovalsky
- Subjects
DNA, Bacterial ,medicine.drug_class ,Immunoprecipitation ,Ultraviolet Rays ,Monoclonal antibody ,medicine.disease_cause ,Biochemistry ,Epitope ,Endonuclease ,chemistry.chemical_compound ,Epitopes ,Bacterial Proteins ,medicine ,Molecular Biology ,Escherichia coli ,chemistry.chemical_classification ,Endodeoxyribonucleases ,biology ,Base Sequence ,DNA, Superhelical ,Escherichia coli Proteins ,DNA Helicases ,Antibodies, Monoclonal ,Cell Biology ,Molecular biology ,Precipitin Tests ,Nucleoprotein ,Amino acid ,chemistry ,biology.protein ,DNA - Abstract
Structural intermediates generated during incision of damaged DNA by the Uvr(A)BC endonuclease were probed with monoclonal antibodies (mAbs) raised against the Escherichia coli UvrB protein. It was found that the epitope of B2C5 mAb, mapped at amino acids (aa) 171–278 of UvrB, is not accessible in any of the preformed Uvr intermediates. Preformed B2C5-UvrB immunocomplexes, however, inhibited formation of those intermediates. B2C5 mAb seems to interfere with the formation of the UvrA-UvrB complex due to overlapping of its epitope and the UvrA binding region of UvrB. Conversely, the epitope of B3C1 mAb (aa 1–7 and/or 62–170) was accessible in all Uvr intermediates. The epitope of B*2E3 mAb (aa 171–278) was not accessible in any of the nucleoprotein intermediates preceding UvrB-DNA preincision complex. However, B*2E3 was able to immunoprecipitate this complex and to inhibit overall incision. B2A1 mAb (aa 8–61) inhibited formation of those Uvr intermediates requiring ATP binding and/or hydrolysis by UvrB. B*2B9 mAb (aa 473–630) inhibited Uvr nucleoprotein complexes involving UvrB. B*2B9 seems to prevent the binding of the UvrA-UvrB complex to DNA. The epitope of the B*3E11 mAb (aa 379–472) was not accessible in Uvr complexes formed at damaged sites. These results are discussed in terms of structure-functional mapping of UvrB protein.
- Published
- 1998
124. Introduction of a tryptophan reporter group into the ATP binding motif of the Escherichia coli UvrB protein for the study of nucleotide binding and conformational dynamics
- Author
-
Lawrence Grossman and Eric L. Hildebrand
- Subjects
Conformational change ,ATP-binding motif ,Protein Conformation ,Proteolysis ,Molecular Sequence Data ,Biology ,Biochemistry ,chemistry.chemical_compound ,Adenosine Triphosphate ,Bacterial Proteins ,medicine ,Escherichia coli ,Nucleotide ,Binding site ,Molecular Biology ,chemistry.chemical_classification ,Adenosine Triphosphatases ,Binding Sites ,medicine.diagnostic_test ,Base Sequence ,Nucleotides ,Escherichia coli Proteins ,Tryptophan ,DNA Helicases ,Cell Biology ,Enzyme Activation ,chemistry ,Mutagenesis ,DNA ,Nucleotide excision repair - Abstract
The DNA-dependent ATPase activity of UvrB is required to support preincision steps in nucleotide excision repair in Escherichia coli. This activity is, however, cryptic. Elicited in nucleotide excision repair by association with the UvrA protein, it may also be unmasked by a specific proteolysis eliminating the C-terminal domain of UvrB (generating UvrB*). We introduced fluorescent reporter groups (tryptophan replacing Phe47 or Asn51) into the ATP binding motif of UvrB, without significant alteration of behavior, to study both nucleotide binding and those conformational changes expected to be essential to function. The inserted tryptophans occupy moderately hydrophobic, although potentially heterogeneous, environments as evidenced by fluorescence emission and time-resolved decay characteristics, yet are accessible to the diffusible quencher acrylamide. Activation, via specific proteolysis, is accompanied by conformational change at the ATP binding site, with multiple changes in emission spectra and a greater shielding of the tryptophans from diffusible quencher. Titration of tryptophan fluorescence with ATP has revealed that, although catalytically incompetent, UvrB can bind ATP and bind with an affinity equal to that of the active UvrB* form (Kd of approximately 1 mM). The ATP binding site of UvrB is therefore functional and accessible, suggesting that conformational change either brings amino acid residues into proper alignment for catalysis and/or enables response to effector DNA.
- Published
- 1998
125. Selection of monoclonal antibodies for probing of functional intermediates in incision of UV-irradiated DNA by Uvr(A)BC endonuclease from Escherichia coli
- Author
-
Oleg I. Kovalsky, Chien-liang Glenn Lin, and Lawrence Grossman
- Subjects
medicine.drug_class ,Ultraviolet Rays ,Biophysics ,Biology ,Monoclonal antibody ,medicine.disease_cause ,Biochemistry ,Binding, Competitive ,Epitope ,Endonuclease ,chemistry.chemical_compound ,Epitopes ,Bacterial Proteins ,Structural Biology ,Genetics ,medicine ,Escherichia coli ,UvrABC endonuclease ,Adenosine Triphosphatases ,Endodeoxyribonucleases ,Escherichia coli Proteins ,DNA Helicases ,Antibodies, Monoclonal ,DNA ,Molecular biology ,DNA-Binding Proteins ,Epitope mapping ,chemistry ,biology.protein ,Nucleotide excision repair - Abstract
Monoclonal antibodies (mAbs) were generated that recognize UvrA and UvrB proteins. These proteins are components of the Uvr(A)BC endonuclease, which initiates nucleotide excision repair in Escherichia coli. mAbs, which can be used for probing of structural intermediates of Uvr(A)BC endonuclease functioning, were selected for their ability to: (i) recognize different epitopes; (ii) have a high-affinity for native antigenic protein; (iii) preserve functionality of the Uvr protein in immunocomplex. The adherence of anti-Uvr mAbs with these criteria was verified by additivity and competition tests, and by their influence on the ATPase activities of UvrA and UvrB*, the functionally active proteolytic fragment of UvrB. Two out of twelve anti-UvrA and seven out of thirteen anti-UvrB/anti-UvrB* hybridoma lines were shown to satisfy these criteria. Recognition of UvrA and UvrB deletion mutant proteins by mAbs was used to map their epitopes. Epitopes of A2D1 and A2B1 mAbs were mapped to regions of amino acids 230–281 and 560–680 of UvrA, respectively. Epitopes of anti-UvrB/UvrB* mAbs were assigned to the following amino acid regions of UvrB: B2A1, 8–61; B2C5 and B*2E3, 171–278; B2E2, 631–673; B3C1, 1–7 and/or 62–170; B*2B9, 473–630; B*3E11, 379–472. The ability of selected mAbs to neutralize the incision function of Uvr(A)BC was analyzed. The results are discussed in terms of the applicability of these mAbs to probe the structures of intermediates in the functioning of Uvr(A)BC.
- Published
- 1998
126. Transcription coupled nucleotide excision repair by isolated Escherichia coli membrane-associated nucleoids
- Author
-
Lawrence Grossman, Oleg I. Kovalsky, and Chien-liang Glenn Lin
- Subjects
DNA, Bacterial ,DNA Repair ,Transcription, Genetic ,DNA damage ,DNA repair ,Ultraviolet Rays ,Pyrimidine dimer ,Biology ,chemistry.chemical_compound ,Bacterial Proteins ,Transcription (biology) ,RNA polymerase ,Genetics ,Escherichia coli ,Nucleoid ,Adenosine Triphosphatases ,Binding Sites ,Membranes ,Escherichia coli Proteins ,DNA-Directed RNA Polymerases ,DNA-Binding Proteins ,Biochemistry ,chemistry ,Genes, Bacterial ,DNA ,Nucleotide excision repair ,Research Article ,DNA Damage - Abstract
One form of nucleotide excision repair (NER) is known to be functionally coupled to transcription, but the nature of this functional link in Escherichia coli is still unclear. Here we have employed the isolated membrane-associated nucleoids from E.coli to examine this issue. We show that the isolated nucleoid fraction is capable of excision of UV-induced pyrimidine dimers when reconstituted with a cytoplasmic fraction resolved by sucrose gradient fractionation. This excision activity by UvrABC is sensitive to rifampicin and is dependent on transcription. By using crosslinking and immunoprecipitation, the damage recognition protein, UvrA, was found to be specifically associated with the RNA polymerase beta subunit on the chromosomal DNA independent of DNA damage. It suggests that at least in one of the NER pathways the search for damage may be directly linked to RNA polymerase. In addition, the role of transcription in the unfolding of the nucleoid structure to allow repair enzymes to gain access to the damaged DNA is described. This study provides insight into the understanding of the transcription-repair coupling in vivo.
- Published
- 1998
127. The effect of donor age on the processing of UV-damaged DNA by cultured human cells: reduced DNA repair capacity and increased DNA mutability
- Author
-
Shin-Ichi Moriwaki, Lawrence Grossman, Robert E. Tarone, Satyajit Ray, and Kenneth H. Kraemer
- Subjects
Adult ,Aging ,Adolescent ,DNA Ligases ,DNA Repair ,DNA damage ,Somatic cell ,DNA repair ,Ultraviolet Rays ,Biology ,Toxicology ,medicine.disease_cause ,chemistry.chemical_compound ,Plasmid ,Genetics ,medicine ,Humans ,Child ,Molecular Biology ,Cells, Cultured ,Aged ,Skin ,Aged, 80 and over ,Mutation ,Mutagenesis ,Transfection ,Fibroblasts ,Middle Aged ,Molecular biology ,DNA-Binding Proteins ,chemistry ,Child, Preschool ,Immunology ,DNA ,DNA Damage - Abstract
Aging in humans carries an increased risk of skin cancer, a disorder linked to somatic mutations in sun damaged skin. DNA repair plays a major role in protection against sun damage. We found an age-related decline in post-UV DNA repair capacity (measured by the ability to repair a UV-treated plasmid (pCMVcat)) of-0.6% per year (p = 0.0001) in cultured primary skin fibroblasts from normal donors from the first to the tenth decade of life. There was a corresponding age-related increase in post-UV mutability (measured as mutations introduced into a transfected, UV-treated plasmid (pSP189)) of +0.6% per year (p = 0.001) in lymphoblastoid cell lines from normal donors of the same age range. This study indicates that aging in humans is associated with decreasing ability to process new UV-induced DNA damage and this age-related reduction in DNA repair capacity and increase in DNA mutability is reflected in cultured skin and blood cells.
- Published
- 1996
128. RNA polymerase signals UvrAB landing sites
- Author
-
Byungchan Ahn and Lawrence Grossman
- Subjects
DNA Repair ,DNA repair ,Protein Conformation ,Ultraviolet Rays ,Molecular Sequence Data ,DNA, Recombinant ,Biochemistry ,chemistry.chemical_compound ,Bacterial Proteins ,Potassium Permanganate ,Transcription (biology) ,RNA polymerase ,Escherichia coli ,Promoter Regions, Genetic ,Molecular Biology ,Transcription bubble ,Adenosine Triphosphatases ,Binding Sites ,biology ,Base Sequence ,Escherichia coli Proteins ,DNA Helicases ,Helicase ,Cell Biology ,DNA-Directed RNA Polymerases ,Molecular biology ,Cell biology ,DNA-Binding Proteins ,enzymes and coenzymes (carbohydrates) ,chemistry ,DNA Topoisomerases, Type I ,biology.protein ,bacteria ,DNA supercoil ,DNA ,Nucleotide excision repair ,Signal Transduction - Abstract
Transcription when coupled to nucleotide excision repair specifies the location in active genes where preferential DNA repair is to take place. During DNA damage-induced recruitment of RNA polymerase (RNAP), there is a physical association of the beta subunit of Escherichia coli RNAP and the UvrA component of the repair apparatus (G. C. Lin and L. Grossman, submitted for publication). This molecular affinity is reflected in the ability of the RNAP to increase, in a promoter-dependent manner, DNA supercoiling by the UvrAB complex. In the presence of the RNAP, the UvrAB complex is able to bind to promoter regions and to translocate in a 5' to 3' direction along the non-transcribed strand. As a consequence of this helicase-catalyzed translocation, preferential incision of DNA damaged sites occurs downstream on the transcribed strand. Because of the helicase directionality, the initial binding of the UvrAB complex to the transcribed strand would inevitably lead to its collision with the RNAP. These results imply that the RNAP-induced DNA structure in the vicinity of the transcription start site signals a landing or entry site for the UvrAB complex on DNA.
- Published
- 1996
129. Supernovae, grains and the formation of the Solar System
- Author
-
Lawrence Grossman, James M. Lattimer, and David N. Schramm
- Subjects
Neon ,Supernova ,Materials science ,Xenon ,chemistry ,Explosive material ,Meteorite ,chemistry.chemical_element ,Astrophysics ,Formation and evolution of the Solar System ,Carbon ,Oxygen - Abstract
An investigation is conducted concerning the possibility that observed Mg-26 anomalies in meteorites may be related to a nucleosynthetic event which preceded the formation of the solar system by at most a few million years. The Al-26, which decayed to form the observed excess Mg-26, could have been produced in either explosive carbon burning or in a high temperature carbon burning shell source immediately preceding the explosion. The results of supernova grain condensation calculations are presented and related to the hypothesis that a 'last event' supernova was indeed related to the formation of the solar system and thus might have created the observed isotopic anomalies in magnesium, oxygen, neon, and xenon.
- Published
- 1996
130. Measurement of DNA repair deficiency in workers exposed to benzene
- Author
-
William W. Au, R el Zein, Lawrence Grossman, and Lance M. Hallberg
- Subjects
Adult ,Chloramphenicol O-Acetyltransferase ,Male ,Xeroderma pigmentosum ,DNA Repair ,DNA damage ,DNA repair ,Ultraviolet Rays ,Health, Toxicology and Mutagenesis ,Biology ,Gene mutation ,medicine.disease_cause ,Host-Cell Reactivation ,Cell Line ,Occupational Exposure ,medicine ,Humans ,Lymphocytes ,Reporter gene ,Mutation ,Public Health, Environmental and Occupational Health ,Benzene ,Middle Aged ,medicine.disease ,Molecular biology ,Chemical Industry ,Female ,Genotoxicity ,DNA Damage ,Plasmids ,Research Article - Abstract
We hypothesize that chronic exposure to environmental toxicants can induce genetic damage causing DNA repair deficiencies and leading to the postulated mutator phenotype of carcinogenesis. To test our hypothesis, a host cell reactivation (HCR) assay was used in which pCMVcat plasmids were damaged with UV light (175, 350 J/m{sup 2} UV light), inactivating the chloramphenicol acetyltransferase reporter gene, and then transfected into lymphocytes. Transfected lymphocytes were therefore challenged to repair the damaged plasmids, reactivating the reporter gene. Xeroderma pigmentosum (XP) and Gaucher cell lines were used as positive and negative controls for the HCR assay. The Gaucher cell line repaired normally but XP cell lines demonstrated lower repair activity. Additionally, the repair activity of the XP heterozygous cell line showed intermediate repair compared to the homozygous XP and Gaucher cells. We used HCR to measure the effects of benzene exposure on 12 exposed and 8 nonexposed workers from a local benzene plant. Plasmids 175 J/m{sup 2} and 350 J/m{sup 2} were repaired with a mean frequency of 66% and 58%, respectively, in control workers compared to 71% and 62% in exposed workers. Conversely, more of the exposed workers were grouped into the reduced repair category than controls. These differences inmore » repair capacity between exposed and control workers were, however, not statistically significant. The lack of significant differences between the exposed and control groups may be due to extremely low exposure to benzene (
- Published
- 1996
131. DNA repair and epidemiology of basal cell carcinoma
- Author
-
Lawrence Grossman and Qingyi Wei
- Subjects
Premature aging ,Adult ,Male ,Pathology ,medicine.medical_specialty ,Aging ,Xeroderma pigmentosum ,Skin Neoplasms ,DNA Repair ,DNA damage ,DNA repair ,Cell Survival ,Ultraviolet Rays ,T-Lymphocytes ,Clinical Biochemistry ,Population ,Biology ,Host-Cell Reactivation ,Cohort Studies ,Sex Factors ,medicine ,Humans ,Point Mutation ,Basal cell carcinoma ,skin and connective tissue diseases ,education ,education.field_of_study ,integumentary system ,Point mutation ,Biochemistry (medical) ,Estrogen Replacement Therapy ,Middle Aged ,medicine.disease ,Genes, p53 ,Gene Expression Regulation ,Carcinoma, Basal Cell ,Cancer research ,Female ,Chromosomes, Human, Pair 9 ,Contraceptives, Oral ,DNA Damage - Abstract
In a molecular epidemiological study of DNA repair, host reactivation assay was used to measure the DNA repair capacity of cryopreserved lymphocytes from 88 primary basal cell carcinoma (BCC) patients and 135 cancer-free controls. In this study population, reduced repair of ultraviolet radiation-induced DNA damage contributed to the risk of sunlight-induced BCC. A family history of BCC is associated with low DNA repair. Repair of ultraviolet radiation-damaged DNA declines at a rate of approximately 1%/year in noncancerous controls. Reduced DNA repair is more likely seen in young BCC patients, indicating that BCC is a premature aging disease of the skin. The persistence of photochemical damage because of reduced repair results in point mutations in the p53 gene and allelic loss of the nevoid BCC gene located on chromosome 9q. Xeroderma pigmentosum appears to be a valid paradigm for the role of DNA repair in BCC in the general population.
- Published
- 1995
132. Damage recognition by UvrABC. A study of vectorial movement
- Author
-
Lawrence Grossman
- Subjects
Endodeoxyribonucleases ,DNA Repair ,Transcription, Genetic ,Movement (music) ,Chemistry ,General Neuroscience ,Escherichia coli Proteins ,Molecular Sequence Data ,General Biochemistry, Genetics and Molecular Biology ,Adenosine Triphosphate ,History and Philosophy of Science ,Amino Acid Sequence ,Neuroscience ,DNA Damage - Published
- 1994
133. RESPONSE: Re: DNA Repair, Dysplastic Nevi, and Sunlight Sensitivity in the Development of Cutaneous Malignant Melanoma
- Author
-
Robert E. Tarone, Lawrence Grossman, Margaret A. Tucker, Mohammad Hedayati, Angela Cecilia Pesatori, Andrea A. Baccarelli, and Maria Teresa Landi
- Subjects
Sunlight ,Cancer Research ,Oncology ,DNA repair ,business.industry ,Melanoma ,Cancer research ,medicine ,Sensitivity (control systems) ,medicine.disease ,business - Published
- 2002
134. Mutations in the helix-turn-helix motif of the Escherichia coli UvrA protein eliminate its specificity for UV-damaged DNA
- Author
-
Jinting Wang and Lawrence Grossman
- Subjects
Protein Conformation ,Ultraviolet Rays ,Mutant ,Molecular Sequence Data ,Helix-turn-helix ,Biology ,Biochemistry ,Substrate Specificity ,chemistry.chemical_compound ,Structure-Activity Relationship ,Protein structure ,Adenosine Triphosphate ,Bacterial Proteins ,Escherichia coli ,Amino Acid Sequence ,Site-directed mutagenesis ,Molecular Biology ,Zinc finger ,Adenosine Triphosphatases ,Base Sequence ,Sequence Homology, Amino Acid ,DNA, Superhelical ,Escherichia coli Proteins ,Hydrolysis ,Wild type ,Zinc Fingers ,Cell Biology ,DNA ,Molecular biology ,DNA-Binding Proteins ,chemistry ,DNA, Viral ,Mutation ,Nucleotide excision repair ,DNA Damage - Abstract
The Escherichia coli UvrA protein possesses a stretch of amino acids, 494 to 513, that matches the consensus sequence of the helix-turn-helix motif of many sequence-specific DNA binding proteins. It also has two zinc finger motif regions and two ATP binding sites. To study the potential roles of both helix-turn-helix and zinc finger motifs in the functioning of UvrA protein, random mutations were created in these motif regions by degenerate oligonucleotide-directed mutagenesis. Using this method, 12 single substitution mutants (eight in the helix-turn-helix motif region, one in the N-terminal zinc finger region, and three in the C-terminal zinc finger region) were isolated that failed to confer UV resistance in the E. coli strain deleted of the uvrA gene. One "hyper" UV-resistant mutant, G275A, was identified that conferred significantly more UV resistance than the wild type in the MH1-delta A strain. To further investigate the mechanism of failure of these mutant UvrA proteins to support nucleotide excision repair, two mutant UvrA proteins, G502D and V508D, were selected for purification and characterization, since they carry mutations at the positions offered as the putative constellation for the helix-turn-helix motif. The binding affinity of these two mutants for nonirradiated plasmid DNA was unaffected by the mutations. Both mutant proteins exhibited substantial ATPase activity, and together with the UvrB protein, they were capable of generating positively supercoiled plasmid DNA from the relaxed form in the presence of ATP and bacterial topoisomerase I. However, both mutant proteins failed to respond to UV damage in the filter binding assay and were incapable of forming 2 x SSC-resistant nucleoprotein complexes with UvrB protein on UV-irradiated plasmid DNA. Taking these properties together, it appears that the mutations in the helix-turn-helix motif region impaired the UvrA protein's ability to recognize UV damage, while its other activities were largely unaffected. Interestingly, ERCC-3, a human DNA repair protein, also has a similar helix-turn-helix motif. Given the highly conserved nature of repair proteins in general, this observation raises the possibility that both procaryotes and eucaryotes might use similar mechanisms to recognize damaged sites in their genomes.
- Published
- 1993
135. The role of DNA damage and its repair in the aging process
- Author
-
Lawrence Grossman
- Subjects
Aging ,DNA Repair ,business.industry ,DNA damage ,DNA repair ,Geriatrics gerontology ,Process (engineering) ,Medicine ,Humans ,Geriatrics and Gerontology ,business ,Cell biology ,DNA Damage - Published
- 1992
136. STRUCTURE-FUNCTION ANALYSES OF Uvr PROTEINS CATALYZING NUCLEOTIDE EXCISION
- Author
-
Lawrence Grossman, Sambasivamoorthy Thiagalingam, Sharlyn J. Mazur, T. Seeley, and Lark Claassen
- Subjects
chemistry.chemical_classification ,Biochemistry ,Chemistry ,Structure function ,Nucleotide - Published
- 1992
137. Dimerization of Escherichia coli UvrA and its binding to undamaged and ultraviolet light damaged DNA
- Author
-
Sharlyn J. Mazur and Lawrence Grossman
- Subjects
DNA Replication ,DNA, Bacterial ,DNA Repair ,DNA repair ,Ultraviolet Rays ,DNA, Single-Stranded ,medicine.disease_cause ,Biochemistry ,Binding, Competitive ,chemistry.chemical_compound ,Endonuclease ,Plasmid ,Adenosine Triphosphate ,Bacterial Proteins ,Ultraviolet light ,medicine ,Escherichia coli ,chemistry.chemical_classification ,Gel electrophoresis ,Adenosine Triphosphatases ,biology ,Escherichia coli Proteins ,Micropore Filters ,Collodion ,DNA-Binding Proteins ,Kinetics ,Enzyme ,chemistry ,biology.protein ,bacteria ,Thermodynamics ,DNA ,DNA Damage - Abstract
The initial stages in the repair of damaged DNA by the Escherichia coli uvr system involve the recognition of damage by UvrA. We have examined in detail the binding of UvrA to DNA randomly damaged by ultraviolet light, undamaged DNA, and single-stranded DNA using nitrocellulose filter binding and gel mobility shift assays to arrive at the following model: UvrA dimers bind specifically to damaged DNA both in the presence and in the absence of ATP. The dimerization of UvrA is promoted by UvrA concentrations greater than 1 nM, the presence of ATP, or physiological temperatures, and the dimerization step dominates the temperature dependence of UvrA binding to DNA damaged by ultraviolet light. The apparent association constant for specific binding is dependent on the concentration of UvrA due to coupled dimerization, aggregation, and nonspecific binding reactions. At 1 nM UvrA, either with or without ATP, Kuv approximately 10(9) M-1. The binding of UvrA to undamaged DNA is 10(3)-10(4)-fold weaker than the damage-specific binding. Both the strength of damage-specific binding and the discrimination between damaged and undamaged sites are affected by the salt concentration. The kinetics of association and dissociation reactions indicate that the primary effects of ATP are on the extent of UvrA dimerization rather than on the properties of the UvrA-uvDNA complex. The complexity of the interaction of UvrA, ATP, and DNA is indicated by the opposing effects of ATP binding and hydrolysis on UvrA dimerization.
- Published
- 1991
138. STRUCTURE-FUNCTION ANALYSES OF Uvr PROTEINS CATALYZING NUCLEOTIDE EXCISION
- Author
-
E-Y. Oh, Sharlyn J. Mazur, T. Seeley, Lawrence Grossman, Sambasivamoorthy Thiagalingam, and Lark Claassen
- Subjects
chemistry.chemical_classification ,Biochemistry ,Chemistry ,Structure function ,Nucleotide - Published
- 1991
139. DNA as a Biosensor for Environmental Agents
- Author
-
Lawrence Grossman and William F. Athas
- Subjects
chemistry.chemical_classification ,chemistry.chemical_compound ,Enzyme ,Chemistry ,DNA damage ,DNA repair ,DNA Modification ,Host-Cell Reactivation ,Biosensor ,Gene ,DNA ,Cell biology - Abstract
It is the thesis of this paper that DNA can be utilized as a target to detect environmental agents that can modify DNA directly or indirectly through metabolic activation. Expression of DNA modification will be achieved by using as a target a bacterial gene encoding an easily assessable enzyme. The modified gene will be physically introduced into DNA repair deficient lymphoid lines. The level of damage will be reflected as loss of gene activity manifested as reduction of the specific enzyme activity. This extremely sensitive and specific assay, in its essence, is a “Host Cell Reactivation” (HCR) in which damaged viruses are repaired by their hosts.
- Published
- 1991
140. The UvrABC endonuclease system of Escherichia coli--a view from Baltimore
- Author
-
Lawrence Grossman and Anthony T. Yeung
- Subjects
DNA Repair ,ATPase ,Molecular Sequence Data ,Toxicology ,medicine.disease_cause ,Models, Biological ,chemistry.chemical_compound ,Sequence Homology, Nucleic Acid ,Genetics ,medicine ,Escherichia coli ,Nucleotide ,Amino Acid Sequence ,Molecular Biology ,UvrABC endonuclease ,chemistry.chemical_classification ,Adenosine Triphosphatases ,Endodeoxyribonucleases ,biology ,Escherichia coli Proteins ,DNA Helicases ,Helicase ,Molecular biology ,Nucleoprotein ,chemistry ,biology.protein ,DNA polymerase I ,DNA ,DNA Damage - Abstract
Nucleotide excision is initiated by the UvrABC endonuclease system in which the initial DNA interaction is with UvrA which was dimerized in the presence of ATP. Nucleoprotein formation most likely takes place on undamaged regions of DNA by (UvrA)2 which has been dimerized in the presence of ATP. Topological unwinding of DNA, driven by ATP binding, is increased by the presence of UvrB to approximately a single helical turn. The Uvr(A)2B complex translocates to a damaged site by the combined Uvr(A)2B helicase in which the driving force is provided by the UvrB-associated ATPase. The dual incision reaction is initiated by the binding of the UvrC protein to the Uvr(A)2B-nucleoprotein complex. The proteins in this post-incision nucleoprotein complex do not turn over and require the presence of the UvrD protein and DNA polymerase I under polymerizing conditions. The final integrity of the DNA strands is restored with polynucleotide ligase.
- Published
- 1990
141. Age Should Be Considered as a Risk Factor for Basal Cell Carcinoma and DNA Repair Capacity
- Author
-
François J. Aubin, Pierre G. Agache, Philippe Humbert, Qingyi Wei, and Lawrence Grossman
- Subjects
Genetics ,DNA repair ,business.industry ,medicine ,Cancer research ,Basal cell carcinoma ,Cell Biology ,Dermatology ,Risk factor ,medicine.disease ,business ,Biochemistry ,Molecular Biology - Published
- 1996
- Full Text
- View/download PDF
142. A Giant in Geochemistry
- Author
-
Lawrence Grossman
- Subjects
Multidisciplinary ,Geochemistry ,Geology - Published
- 1993
143. Thymidine dinucleotide enhances DNA repair in human skin cells
- Author
-
T Maeda, M Gleason, Mohammad Hedayati, Barbara A. Gilchrest, Eller, and Lawrence Grossman
- Subjects
chemistry.chemical_compound ,Chemistry ,DNA repair ,Human skin ,Dermatology ,Thymidine ,Molecular Biology ,Biochemistry ,Molecular biology - Published
- 1998
144. Epidemiology of Ultraviolet-DNA Repair Capacity and Human Cancer
- Author
-
Lawrence Grossman
- Subjects
Premature aging ,Male ,Aging ,Xeroderma pigmentosum ,Neoplasms, Radiation-Induced ,DNA Repair ,DNA damage ,DNA repair ,Ultraviolet Rays ,Health, Toxicology and Mutagenesis ,Population ,Biology ,medicine.disease_cause ,Sex Factors ,Risk Factors ,medicine ,Humans ,Basal cell carcinoma ,education ,skin and connective tissue diseases ,Genetics ,Mutation ,education.field_of_study ,integumentary system ,Point mutation ,Public Health, Environmental and Occupational Health ,DNA ,medicine.disease ,Cancer research ,Sunlight ,Female ,Research Article - Abstract
The following conclusions are derived from an epidemiological study. Reduced repair of ultraviolet (UV)-induced DNA damage contributes directly to basal cell carcinoma (BCC) in individuals with prior sunlight overexposure. A family history of BCC is a predictor of low DNA repair. Repair of UV-damaged DNA declines at a fixed rate of approximately 1% per annum in noncancerous controls. The DNA repair differences between young BCC cases and their controls disappear as they age. Hence, BCC, in terms of DNA repair, is a premature aging disease. The persistence of photochemical damage because of reduced repair results in point mutations in the p53 gene and allelic loss of the nevoid BCC gene (Gorlin's syndrome) located on chromosome 9q. The fact that environmental vulnerability is gender oriented implicates hormones in regulating DNA repair. Xeroderma pigmentosum appears to be a valid paradigm for the role of DNA repair in BCC in the general population.
- Published
- 1997
145. DNA repair and breast carcinoma susceptibility in women.
- Author
-
Juan M. Ramos, Abigail Ruiz, Rivka Colen, Ivette D. Lopez, Lawrence Grossman, and Jaime L. Matta
- Published
- 2004
146. Corrections: DNA Repair and Aging in Basal Cell Carcinoma: A Molecular Epidemiology
- Author
-
Qingyi Wei, Mohammad Hedayati, Genevieve M. Matanoski, Evan R. Farmer, and Lawrence Grossman
- Subjects
Multidisciplinary ,Molecular epidemiology ,DNA repair ,medicine ,Basal cell carcinoma ,Biology ,medicine.disease ,Cell biology - Published
- 1993
147. The Jewish Family: Metaphor and Memory. David Kraemer
- Author
-
Lawrence Grossman
- Subjects
Metaphor ,media_common.quotation_subject ,Judaism ,Religious studies ,Sociology ,media_common - Published
- 1990
148. Refractory Inclusions in the Allende Meteorite
- Author
-
Lawrence Grossman
- Subjects
Petrography ,Grossite ,Allende meteorite ,Space and Planetary Science ,Chondrite ,Earth and Planetary Sciences (miscellaneous) ,Geochemistry ,Astronomy and Astrophysics ,Planetary Evolution ,Chemical composition ,Geology ,Refractory (planetary science) ,Isotopic composition - Abstract
The literature on the coarse-grained inclusions of the Allende meteorite is reviewed, with attention given to petrography and major minerals, micromineralogy and microtextures, bulk chemical composition, and isotopic composition. It is concluded that the coarse-grained inclusions provide evidence for a supernova explosion that occurred just before condensation, for incompletely homogenized material from several nucleosynthetic sources, and for solar nebular regions of different chemical and isotopic composition.
- Published
- 1980
149. 'Fluffy' Type A Ca-, Al-rich inclusions in the Allende meteorite
- Author
-
Lawrence Grossman and Glenn J. MacPherson
- Subjects
Allende meteorite ,Meteorite ,Geochemistry and Petrology ,Chondrite ,engineering ,Mineralogy ,Melilite ,Hibonite ,Pyroxene ,engineering.material ,Formation and evolution of the Solar System ,Anorthite ,Geology - Abstract
Inclusions called 'fluffy' Type A's or FTA's in the Allende meteorite are examined as possible candidates for relict vapor-solid condensate grains, remaining from the original solar nebula. Type A inclusions are characterized by abundant melilite and absence of primary anorthite and titaniferous pyroxene. Fluffy Type A's were probably loosely bound clumps of crystals drifting in the solar nebula, analogous to dustballs or snowflakes. Polished thin sections of all samples were studied optically and with a JEOL JSM-35 scanning electron microscope. It is reasonably clear that neither whole FTA's nor constituent nodules of the coarser grained ones were ever molten. Despite solid-state recrystallization which has affected these inclusions to varying degrees, the coarser grained material remaining in many of them is probably a relic of vapor-solid condensation in the solar nebula.
- Published
- 1984
150. Determination of trace element mineral/liquid partition coefficients in melilite and diopside by ion and electron microprobe techniques
- Author
-
J. R. Laughlin, M. L. Johnson, D. S. Burnett, S. M. Kuehner, and Lawrence Grossman
- Subjects
Microprobe ,Diopside ,Chemistry ,Analytical chemistry ,Mineralogy ,Melilite ,Electron microprobe ,engineering.material ,Ion ,Crystal ,Partition coefficient ,Geochemistry and Petrology ,visual_art ,engineering ,visual_art.visual_art_medium ,Chemical composition - Abstract
The use of the ion microprobe for quantitative analysis of Sr, Y, Zr, La, Sm, and Yb in melilite and pyroxene is evaluated. Three trace element-doped synthetic glasses of composition Ak_40, Ak_80, and Di_2AbAn were analyzed by ion microprobe (IMP) using ion yields determined from Corning glass standards. IMP-determined oxide concentrations in the Di_2AbAn glass agree well with electron microprobe (EMP) analyses (to within 6%), but IMP analyses of the melilite glasses deviate from EMP averages by up to 19%. The deviations are due to erroneous SiO_2 estimates caused by suppression of Si ion intensities by the enhanced concentrations of Ca and Al in the melilite glasses compared to the standards. Thus, in order to determine compositions of melilite, diopside, and glass from subliquidus experiments on each of the three starting compositions, we adopted a new set of ion yields such that IMP analyses of the three starting glasses reproduce the EMP average compositions. Further IMP and EMP comparisons of the subliquidus assemblages show that quantitative analyses of melilite, diopside, and glass can be obtained by IMP that are within 10% of the concentrations obtained by EMP, when ion yields determined from glass starting compositions are used. EMP-IMP comparison of crystal and glass analyses also suggests that a structural matrix effect may result in overestimation of SrO (10–12%) in melilite by IMP. Comparison of our data for Ak_12 and Ak_90 melilite compositions with literature results shows that melilite/liquid for REE^3+ determined by IMP decrease with increasing X_Ak (Ak_90: D_La = 0.038, D_Sm = 0.032, D_Yb = 0.0086; Ak: 0.67, 0.75, 0.25, respectively) while that for Sr (=Eu^2+) changes only slightly (0.99 to 0.78, respectively). Since X_Ak increases with decreasing temperature for all melilite with X_Ak
- Published
- 1989
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.