Mutagenic activity of aziridinyl steroids and their mechanism of action in biological systems.
The aziridinyl derivatives of steroids, structurally related to cholesterol, were tested for their mutagenic activity in the Ames tester strains. The test compounds were mutagenic without metabolic activation, although metabolic activation markedly enhanced their activity. A significant decrease in the survival of SOS defective mutants, recA and lexA of Escherichia coli was observed as compared with their wild-type counterpart in the presence of the steroids. The role of SOS repair genes gains further support from the lambda prophage induction in the lysogen and beta-galactosidase induction in the Mud strains as well as mutagenesis with Ames tester strains. Structural features which appear essential for mutagenic activity in these strains are (i) a reactive N-aminophthalamide group at the (5,6-b) position and (ii) an acetoxy/chlorine group at the third position of the steroidal nucleus. The individual moieties/groups were not mutagenic per se. These steroids appear to generate H2O2 as well as superoxide and hydroxyl radicals in the model biological system.
Islam
S
S
Department of Biochemistry, Faculty of Life Sciences, Aligarh Muslim University, India.
Ahmad
M
M
D001388:Aziridines / Q000737:chemistry / Q000378:metabolism / Q000633:toxicity*; D001564:Benzo(a)pyrene / Q000633:toxicity; D001711:Biotransformation; D002374:Catalase / Q000494:pharmacology; D002777:Cholestanols / Q000737:chemistry / Q000378:metabolism / Q000633:toxicity*; D004790:Enzyme Induction; D004926:Escherichia coli / Q000235:genetics; D016166:Free Radical Scavengers; D009152:Mutagenicity Tests; D009153:Mutagens; D013014:SOS Response, Genetics; D012486:Salmonella typhimurium / Q000235:genetics; D013256:Steroids / Q000737:chemistry / Q000378:metabolism / Q000633:toxicity*; D013482:Superoxide Dismutase / Q000494:pharmacology; D014775:Virus Activation; D001616:beta-Galactosidase / Q000096:biosynthesis
D001388:Aziridines; D002777:Cholestanols; D016166:Free Radical Scavengers; D009153:Mutagens; D013256:Steroids; C071679:3-acetoxycholestanol(5,6-b)(N-phthalimido)aziridine; D001564:Benzo(a)pyrene; D002374:Catalase; D013482:Superoxide Dismutase; D001616:beta-Galactosidase