Human glutathione S-transferase theta (GSTT1): cDNA cloning and the characterization of a genetic polymorphism
Autor: | J B Taylor, S. R. Spencer, Hermann M. Bolt, K R Schroeder, Brian Ketterer, S E Pemble, David J. Meyer, E. Hallier |
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Rok vydání: | 1994 |
Předmět: |
DNA
Complementary Molecular Sequence Data Population Molecular cloning Biochemistry Isozyme Polymorphism (computer science) Complementary DNA Animals Humans Amino Acid Sequence Cloning Molecular education Molecular Biology Glutathione Transferase Southern blot Genetics education.field_of_study Polymorphism Genetic Base Sequence biology Nucleic acid sequence Cell Biology Molecular biology Rats Isoenzymes Glutathione S-transferase biology.protein Research Article |
Zdroj: | Biochemical Journal. 300:271-276 |
ISSN: | 1470-8728 0264-6021 |
DOI: | 10.1042/bj3000271 |
Popis: | In humans, glutathione-dependent conjugation of halomethanes is polymorphic, with 60% of the population classed as conjugators and 40% as non-conjugators. We report the characterization of the genetic polymorphism causing the phenotypic difference. We have isolated a cDNA that encodes a human class Theta GST (GSTT1) and which shares 82% sequence identity with rat class Theta GST5-5. From PCR and Southern blot analyses, it is shown that the GSTT1 gene is absent from 38% of the population. The presence or absence of the GSTT1 gene is coincident with the conjugator (GSST1+) and non-conjugator (GSTT1-) phenotypes respectively. The GSTT1+ phenotype can catalyse the glutathione conjugation of dichloromethane, a metabolic pathway which has been shown to be mutagenic in Salmonella typhimurium mutagenicity tester strains and is believed to be responsible for carcinogenicity of dichloromethane in the mouse. In humans, the enzyme is found in the erythrocyte and this may act as a detoxification sink. Characterization of the GSTT1 polymorphism will thus enable a more accurate assessment of human health risk from synthetic halomethanes and other industrial chemicals. |
Databáze: | OpenAIRE |
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