Induction of 8-hydroxy-2-deoxyguanosine and single-strand breaks in DNA of V79 cells by tetrachloro-p-hydroquinone.
The biocide pentachlorophenol (PCP) is in part metabolized, by microsomal enzymes, to tetrachloro-p-hydroquinone (TCHQ), which easily oxidizes to its semiquinone radical. Redox cycling of this compound produces reactive oxygen species (ROS) which ultimately may damage cellular DNA. Here, we report on DNA damage generated by TCHQ in hamster lung fibroblasts (V79 cells) using 8-hydroxy-2-deoxyguanosine (8-OH-dG) as a marker of a major oxidative genetic lesion and measuring the induction of DNA single-strand breaks (DNA SSB) with the aid of the alkaline elution assay. TCHQ was administered to cell cultures in concentrations of 6.25, 12.5, 25, and 50 microM for 1 h. 6.25 and 12.5 microM had no significant effect on both parameters, whereas the higher concentrations resulted in increases of the level of 8-OH-dG (2.3- and 2.0-fold, respectively) and induced DNA SSB. The latter lesion may arise from (i) direct attack of OH., (ii) repair of hydroxylated DNA bases, or (iii) cytotoxic effects. Metabolic transformation of PCP to TCHQ and/or other metabolites with quinoid structures and the subsequent generation of ROS, producing oxidative DNA damage, may play a role in PCP-induced carcinogenicity observed in mice.
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; D002478:Cells, Cultured; D006224:Cricetinae; D003412:Cricetulus; D004249:DNA Damage; D004277:DNA, Single-Stranded / Q000187:drug effects; D003849:Deoxyguanosine / Q000031:analogs & derivatives* / Q000096:biosynthesis; D004305:Dose-Response Relationship, Drug; D005347:Fibroblasts / Q000187:drug effects; D006873:Hydroquinones / Q000633:toxicity*; D017665:Hydroxyl Radical; D016018:Least-Squares Analysis; D008168:Lung / Q000166:cytology / Q000187:drug effects; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D010416:Pentachlorophenol / Q000378:metabolism / Q000633:toxicity; D017382:Reactive Oxygen Species / Q000378:metabolism / Q000633:toxicity
D002274:Carcinogens, Environmental; D004277:DNA, Single-Stranded; D006873:Hydroquinones; D017382:Reactive Oxygen Species; D017665:Hydroxyl Radical; C044578:2,3,5,6-tetrachlorohydroquinone; D000080242:8-Hydroxy-2'-Deoxyguanosine; D010416:Pentachlorophenol; D003849:Deoxyguanosine