Clastogenic and mutagenic actions of active species generated in the 6-hydroxydopamine/oxygen reaction: effects of scavengers of active oxygen, iron, and metal chelating agents.
A pro-oxidant triphenol, 6-hydroxydopamine (6-OHDA), induced mutations in the Salmonella typhimurium TA 104 tester strain (over the concentration range to 800 microM), and induced chromosomal aberrations in cultured Chinese hamster ovary (CHO) cells at lower concentrations (up to 90 microM). It was however only marginally mutagenic (up to cytotoxic levels of 200 microM) in the TA102 tester strain. Clastogenicity in the more sensitive CHO cell assay was mediated by activated oxygen. Superoxide dismutase decreased the incidence of chromosomal aberrations by 60% and catalase (or superoxide dismutase plus catalase) decreased the incidence to control levels. The clastogenicity of 6-OHDA was dependent upon unsequestered transition metal ions, since addition of EDTA plus desferrioxamine decreased chromosomal aberrations by 90%. The simplest explanation of the data is that genotoxicity is mediated by active species generated in a Fenton-type reaction between 6-OHDA and H2O2 catalyzed by traces of metals in the medium.
Gee
P
P
Environmental Carcinogenesis Unit, B.C. Cancer Research Center, Vancouver, Canada.
San
R H
RH
Davison
A J
AJ
Stich
H F
HF
D000818:Animals; D016466:CHO Cells / Q000187:drug effects*; D002374:Catalase / Q000494:pharmacology; D002614:Chelating Agents / Q000494:pharmacology*; D002869:Chromosome Aberrations; D006224:Cricetinae; D003412:Cricetulus; D004249:DNA Damage; D016166:Free Radical Scavengers; D006861:Hydrogen Peroxide / Q000378:metabolism; D007501:Iron / Q000494:pharmacology*; D016296:Mutagenesis; D009152:Mutagenicity Tests; D010084:Oxidation-Reduction; D016627:Oxidopamine / Q000378:metabolism*; D010100:Oxygen / Q000378:metabolism*; D012486:Salmonella typhimurium / Q000187:drug effects*; D013482:Superoxide Dismutase / Q000494:pharmacology
D002614:Chelating Agents; D016166:Free Radical Scavengers; D016627:Oxidopamine; D006861:Hydrogen Peroxide; D007501:Iron; D002374:Catalase; D013482:Superoxide Dismutase; D010100:Oxygen