Oxidative DNA damage and cell proliferation in the livers of B6C3F1 mice exposed to pentachlorophenol in their diet.
Pentachlorophenol (PCP), which has been used as a wood preservative, was reported to be a liver carcinogen in mice. To investigate the initial effects of PCP administration under the same conditions of exposure as in the carcinogenic study, we examined oxidative stress and cell proliferation, along with other hepatotoxicological parameters, in the livers of B6C3F1 mice fed PCP in their diet at doses of 0.03, 0.06, and 0.12% for up to 4 weeks. We observed significant increases of 8-OHdG levels in hepatic nuclear DNA at doses of 0.03% and above at 2 and 4 weeks. Likewise, dose-dependent increases in the labeling index of cells were detected by counting those that had incorporated 5-bromo-2'-deoxyuridine throughout the experimental period. Also, we found significant elevations of the liver weights, concurrent with increases in hepatic DNA content in the treated mice, which again were dose-related. Serum aspartic transferase activity at doses of 0.06% and above were significantly increased despite these changes being slight. Also, histopathological examination provided no evidence of necrotic changes, but severe hepatocyte swelling in the treated mouse livers. These data indicate that PCP might be able to induce cell proliferation in the mouse liver, as well as induce oxidative DNA damage, suggesting both changes may play an important role in hepatocarcinogenesis.
Umemura
T
T
Division of Toxicology, National Institute of Health Sciences, Tokyo, Japan.
Sai-Kato
K
K
Takagi
A
A
Hasegawa
R
R
Kurokawa
Y
Y
D000818:Animals; D001835:Body Weight; D002455:Cell Division; D004247:DNA / Q000187:drug effects; D004249:DNA Damage; D004305:Dose-Response Relationship, Drug; D008099:Liver / Q000187:drug effects* / Q000473:pathology; D008297:Male; D051379:Mice; D009929:Organ Size; D010416:Pentachlorophenol / Q000008:administration & dosage / Q000633:toxicity*
D004247:DNA; D010416:Pentachlorophenol