Oxidative DNA lesions in V79 cells mediated by pentachlorophenol metabolites.
Incubation of the pentachlorophenol (PCP) metabolites, tetrachloro-p-benzoquinone (chloranil, TCpBQ), tetrachloro-p-hydroquinone (TCpHQ) and tetrachloro-p-benzoquinone (TCoBQ) with V79 Chinese hamster cells led to a significant enhancement of the amount of 8-hydroxydeoxyguanosine (8-OH-dG) in DNA. With PCP itself and the metabolite tetrachloro-o-hydroquinone (TCoHQ) no distinct induction of this lesion could be observed. The average yields of 8-OH-dG were about 2-2.5 times above background levels. In addition, TCpBQ and TCpHQ were able to generate DNA single-strand breaks, while PCP, TCoHQ and TCoBQ failed to induce this lesion. All incubations were performed for 1 h without exogenous metabolic activation and concentrations were 25 microM of the respective agent. It is concluded that these metabolites may contribute to the carcinogenicity of PCP observed in mice, by generating reactive oxygen species (ROS) through their redox cycling properties.
Dahlhaus
M
M
Division for Plant Protection Products and Pesticides, Federal Institute for Health Protection of Consumers and Veterinary Medicine, Berlin, Germany.
Almstadt
E
E
Henschke
P
P
Lüttgert
S
S
Appel
K E
KE
D000080242:8-Hydroxy-2'-Deoxyguanosine; D000818:Animals; D002274:Carcinogens, Environmental / Q000378:metabolism / Q000633:toxicity; D002460:Cell Line; D002703:Chloranil / Q000031:analogs & derivatives* / Q000633:toxicity*; D006224:Cricetinae; D004247:DNA / Q000187:drug effects*; D004249:DNA Damage; D004277:DNA, Single-Stranded / Q000187:drug effects; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000032:analysis; D006873:Hydroquinones / Q000633:toxicity*; D051379:Mice; D010416:Pentachlorophenol / Q000378:metabolism*; D017382:Reactive Oxygen Species
D002274:Carcinogens, Environmental; D004277:DNA, Single-Stranded; D006873:Hydroquinones; D017382:Reactive Oxygen Species; D002703:Chloranil; C044578:2,3,5,6-tetrachlorohydroquinone; D000080242:8-Hydroxy-2'-Deoxyguanosine; D004247:DNA; D010416:Pentachlorophenol; D003849:Deoxyguanosine; C039499:2-chloranil