Pentachlorophenol-induced oxidative DNA damage in mouse liver and protective effect of antioxidants.
8-Hydroxydeoxyguanosine (8-OH-dG) was determined as a marker of oxidative DNA damage in male B6C3F1 mice treated with the hepatocarcinogen pentachlorophenol (PCP). A single oral administration of PCP (0-80 mg/kg) significantly and dose-dependently increased the 8-OH-dG level specifically in the liver at 6 hr. Repeated doses (0-80 mg/kg) over 5 days caused a further increase. Elevation of the 8-OH-dG level caused by a single dose of PCP (60 mg/kg) was not affected by ip injection of buthionine sulfoximine (2 mmol/kg), an inhibitor of GSH synthesis, or aminotriazole (1 g/kg), an inhibitor of catalase, showing no clear evidence for enhancement by the oxidative stress due to reduction of antioxidative factors under these experimental conditions. However, examination of the effects of natural antioxidants on repeated PCP treatment (60 mg/kg/day, for 5 days) revealed that oral administration of vitamin E and diallyl sulfide 3 hr before each PCP challenge significantly protected against elevation of hepatic 8-OH-dG levels. beta-Carotene did not have any effect. Ellagic acid, epigallocatechin gallate and vitamin C demonstrated partial protection. These findings indicate that PCP causes oxidative DNA damage in the target organ liver which can be blocked by a number of antioxidant agents.
Sai-Kato
K
K
Division of Toxicology, National Institute of Health Sciences, Tokyo, Japan.
Umemura
T
T
Takagi
A
A
Hasegawa
R
R
Tanimura
A
A
Kurokawa
Y
Y
D000080242:8-Hydroxy-2'-Deoxyguanosine; D000640:Amitrole / Q000494:pharmacology; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D019328:Buthionine Sulfoximine; D004249:DNA Damage; D003849:Deoxyguanosine / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors / Q000378:metabolism; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008717:Methionine Sulfoximine / Q000031:analogs & derivatives / Q000494:pharmacology; D051379:Mice; D010084:Oxidation-Reduction; D010416:Pentachlorophenol / Q000008:administration & dosage / Q000009:adverse effects*; D013997:Time Factors
D000975:Antioxidants; D008717:Methionine Sulfoximine; D019328:Buthionine Sulfoximine; D000080242:8-Hydroxy-2'-Deoxyguanosine; D010416:Pentachlorophenol; D003849:Deoxyguanosine; D000640:Amitrole