Evaluation of the genotoxic properties of paraquat in V79 Chinese hamster cells.
The genotoxic potential of the herbicide paraquat (PQ), an intracellular generator of superoxide, was comparatively tested in various genotoxicity tests with V79 Chinese hamster cells. PQ clearly induced cytotoxicity and chromosome aberrations but did not induce gene mutations at the HPRT locus or increased DNA migration in the comet assay under the same treatment conditions. Using a modified comet assay protocol with formamidopyrimidine-DNA glycosylase (FPG) protein, a DNA repair enzyme which specifically nicks DNA at sites of 8-oxo-guanines and formamidopyrimidines, we could not detect oxidative DNA base damage after PQ treatment. When cells were treated directly on the slides after lysis (i.e, after the cell membrane barrier was eliminated), increased DNA migration was observed after treatment with high PQ-concentrations. Our results suggest that PQ does not significantly induce DNA lesions relevant for HPRT gene mutations in cultivated V79 cells. Since PQ-induced chromosome aberrations only occur after treatment with high concentrations which totally prevent cell survival and are not preceded by an induction of DNA strand breakage in intact cells, their biological significance has to be questioned.
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Universität Ulm-Klinikum, Abteilung Medizinische Genetik, Germany.
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Hartmann
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D000818:Animals; D002460:Cell Line / Q000187:drug effects / Q000648:ultrastructure; D002470:Cell Survival; D002869:Chromosome Aberrations; D006224:Cricetinae; D003412:Cricetulus; D004305:Dose-Response Relationship, Drug; D006540:Herbicides / Q000633:toxicity*; D009152:Mutagenicity Tests; D009153:Mutagens / Q000633:toxicity*; D010269:Paraquat / Q000633:toxicity*
D006540:Herbicides; D009153:Mutagens; D010269:Paraquat