Increased synthesis of glutathione S-transferases in response to anticarcinogenic antioxidants. Cloning and measurement of messenger RNA.

摘要: Glutathione S-transferase activities in mouse hepatic cytosols are elevated as much 11-fold following the administration of BHA (2(3)-tert-butyl-4-hydroxyanisole), a widely used antioxidant food additive. Ethoxyquin (1,2-dihydro-6-ethoxy-2,2,4-trimethylquinoline) and disulfiram [bis(diethyldithiocarbamyl)disulfide] also enhance glutathione S-transferases certain other enzymes. Each these compounds protects rodents against mutagenic carcinogenic metabolites. A major (pI 8.7) minor 9.3) component family have been purified to homogeneity. These transferases immunologically cross-reactive, high degree NH2-terminal sequence homology (but not identical). The enzymes differ number molecular catalytic properties. 12-fold by dietary demonstrated immunotitration. mRNA for is increased more than 20-fold liver RNA BHA-fed mice, determined translation total characterization products immunoprecipitation sodium dodecyl sulfate-gel electrophoresis or two-dimensional gel electrophoresis. cDNA plasmid complementary was constructed. Translation selected hybridization with this gave similar identical polypeptides. insert has partially sequenced its orientation determined. Its corresponds region (beginning at residue 9) amino acid pI 9.3. Hybridization 32P-labeled indicates 26-fold increase homologous response feeding BHA.