Conjugation of carcinogens by 6 class glutathione S-transferases : mechanisms and relevance to variations in human risk

Guengerich, F. Peter, Thier, Ricarda, Persmark, Magnus, Taylor, John B., & Pemble, Sally E. (1995) Conjugation of carcinogens by 6 class glutathione S-transferases : mechanisms and relevance to variations in human risk. Pharmacogenetics and Genomics, 5(SPEC. ), S103-S107.

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Abstract

Conjugation of chemicals with glutathione (GSH) can lead to decreased or increased toxicity. A genetic deficiency in the GSH S-transferase μ class gene M1 has been hypothesized to lead to greater risk of lung cancer in smokers. Recently a gene deletion polymorphism involving the human θ enzyme T1 has been described; the enzyme is present in erythrocytes and can be readily assayed. A rat θ class enzyme, 5-5, has structural and catalytic similarity and the protein was expressed in the Salmonella typhimurium tester strain TA1535. Expression of the cDNA vector increased the mutagenicity of ethylene dibromide and several methylene dihalides. Mutations resulting from the known GSH S-transferase substrate 1,2-epoxy-3-(4′nitrophenoxy)propane were decreased in the presence of the transferase. Expression of transferase 5-5 increased mutations when 1,2,3,4-diepoxybutane (butadiene diepoxide), 4-bromo-1,2-epoxybutane, or 1,3-dichloracetone were added. The latter compound is a model for the putative 1,2-dibromo-3-chloropropane oxidation product 1-bromo-3-chloroacetone. These genotoxicity and genotyping assays may be of use in further studies of the roles of GSH S-transferase θ enzymes in bioactivation and detoxication and any changes in risk due to polymorphism.

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ID Code: 77471
Item Type: Journal Article
Refereed: Yes
Keywords: bromo 3 chloroacetone, dibromo 3 chloropropane, dibromoethane, epoxy 3 (4' nitrophenoxy)propane, dichloroacetone, bromo 1, epoxybutane, butadiene diepoxide, carcinogen, complementary dna, glutathione transferase, isoenzyme, methylene dihalide, unclassified drug, cancer risk, conference paper, conjugation, controlled study, detoxification, erythrocyte, gene expression, genetic polymorphism, human, human cell, metabolic activation, mutagenicity, mutation, nonhuman, priority journal, salmonella typhimurium, xenobiotic metabolism, Animal, Carcinogens, Isoenzymes, Metabolic Detoxication, Drug, Mutagenicity Tests, Neoplasms, Polymorphism (Genetics), Rats, Recombinant Proteins, Risk Factors, Typhimurium
ISSN: 1744-6872
Divisions: Current > Schools > School of Clinical Sciences
Current > QUT Faculties and Divisions > Faculty of Health
Copyright Owner: © 1995 Lippincott Williams & Wilkins
Deposited On: 17 Oct 2014 01:32
Last Modified: 17 Oct 2014 01:32

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