The mechanism of cytogenetic genotoxicity of exogenous glutathione in V-79 cells in vitro--implication of hydrogen peroxide and general traits of oxidative chromosome damage.
The mechanism of cytogenetic genotoxicity (clastogenicity, induction, cell cycle delay) of 10(-3) M glutathione in V79-E cells, as described by Thust and Bach (1985), was studied in detail by using different treatment conditions. It was found that 1-cystine is the essential cofactor in the incubation system. Catalase, but not superoxide dismutase, abolished the genotoxic effect, and the iron chelator desferoxamine, as well as the hydroxyl radical scavenger mannitol, diminished the activity. It is suggested that glutathione, in combination with V79-E cells and cystine, forms a hydrogen peroxide-generating system which provokes the adverse effects. Glutathione as well as 1-cysteine and 2-mercaptopropionylglycine, which were checked for comparison, show a "paradoxic genotoxicity," i.e., at 10(-2) M the effects return almost to the level of controls. Concentration dependence and other criteria of cytogenetic genotoxicity observed with glutathione show obvious similarities to those of other oxidatively acting agents and reveal striking differences to the cytogenetic effects of "typical" genotoxins.
Thust
R
R
Institute of Pathological Anatomy, Medical Academy of Erfurt, German Democratic Republic.
D000818:Animals; D002453:Cell Cycle / Q000187:drug effects; D002478:Cells, Cultured; D002869:Chromosome Aberrations / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005978:Glutathione / Q000633:toxicity*; D006168:Guinea Pigs; D009152:Mutagenicity Tests; D051381:Rats
D005978:Glutathione