Genotoxicity of 1,4-benzoquinone and 1,4-naphthoquinone in relation to effects on glutathione and NAD(P)H levels in V79 cells.
1,4-Benzoquinone is cytotoxic in V79 Chinese hamster cells and induces gene mutations and micronuclei. The cell-damaging effects of quinones are usually attributed to thiol depletion, oxidation of NAD(P)H, and redox-cycling involving the formation of semiquinone radicals and reactive oxygen species. To elucidate the role of these mechanisms in the genotoxicity of 1,4-benzoquinone, we measured various genotoxic effects, cytotoxicity, and the levels of glutathione, NADPH, NADH, and their oxidized forms all in the same experiment. 1,4-Naphthoquinone, which does not induce gene mutations in V79 cells, was investigated for comparative reasons. The quinones had a similar effect on the levels of cofactors. Total glutathione was depleted, but levels of oxidized glutathione were slightly increased. The levels of NADPH and NADH were reduced at high concentrations of the quinones with a simultaneous increase in the levels of NADP+ and NAD+. Both compounds induced micronuclei, but neither increased the frequency of sister chromatid exchange. Only 1,4-benzoquinone induced gene mutations. This effect was observed at low concentrations, where none of the other parameters studied was affected. When the cells were depleted of glutathione prior to treatment with the quinones, the induction of gene mutations and micronuclei remained virtually unchanged. We conclude that a) induction of micronuclei and glutathione depletion by the two quinones are not linked causally, b) 1,4-benzoquinone induces gene mutations by a mechanism different from oxidative stress and glutathione depletion, and c) glutathione does not fully protect the cells against the genotoxicity of quinones.
Ludewig
G
G
Institute of Toxicology, University of Mainz, West Germany.
Dogra
S
S
Glatt
H
H
D000818:Animals; D016227:Benzoquinones; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D005978:Glutathione / Q000378:metabolism*; D009152:Mutagenicity Tests; D009153:Mutagens; D009243:NAD / Q000378:metabolism*; D009249:NADP / Q000378:metabolism*; D009285:Naphthoquinones / Q000633:toxicity*; D010084:Oxidation-Reduction; D011809:Quinones / Q000633:toxicity*
D016227:Benzoquinones; D009153:Mutagens; D009285:Naphthoquinones; D011809:Quinones; D009243:NAD; C004532:quinone; D009249:NADP; D005978:Glutathione; C035342:1,4-naphthoquinone