DNA
oxidation damage has been regarded as one of the possible mechanisms
for the hepatic carcinogenesis of dioxin-like compounds (DLCs). In
this study, we evaluated the toxic equivalency factor (TEF) from the
standpoint of induced DNA oxidation products and their relationship
to toxicity and carcinogenicity. Nine DNA oxidation products were
analyzed in the liver of female Sprague–Dawley rats exposed
to 2,3,7,8-tetrachlorodibenzo-pdioxin (TCDD) alone or the tertiary
mixture of TCDD, 3,3′,4,4′,5-pentachlorobiphenyl (PCB
126), and 2,3,4,7,8-pentachlorodibenzofuran (PeCDF) by gavage
for 14, 31, and 53 weeks (5 days/week) by LC–MS/MS: 8-oxo-7,8-dihydro-2′-deoxyguanosine
(8-oxo-dGuo); 1,N6-etheno-2′-deoxyadenosine
(1,N6-εdAdo); N2,3-ethenoguanine (N2,3-εG);
7-(2-oxoethly)guanine (7-OEG); 1,N2-etheno-2′-deoxyguanosine
(1,N2-εdGuo); malondialdehyde (M1dGuo); acrolein (AcrdGuo); crotonaldehyde (CrdGuo); and 4-hydroxynonenal
(HNEdGuo) derived 2′-deoxyguanosine adducts. Exposure to TCDD
(100 ng/kg/day) significantly induced 1,N6-εdAdo at 31 and 53 weeks, while no increase of 8-oxo-dGuo
was observed. Significant increases were observed for 8-oxo-dGuo and
1,N6-εdAdo at all time points following
exposure to the tertiary mixture (TEQ 100 ng/kg/day). Exposure to
TCDD for 53 weeks only significantly increased 1,N6-εdAdo, while increases of N2,3-εG and 7-OEG were only found in the highest dose
group (100 ng/kg/day). Exposure to the tertiary mixture for 53 weeks
had no effect on N2,3-εG in any
exposure group (TEQ 0, 22, 46, or 100 ng/kg/day), while significant
increases were observed for 1,N6-εdAdo
(all dose groups), 8-oxo-dGuo (46 and 100 ng/kg/day), and 7-OEG (100
ng/kg/day). While no significant increase was observed at 53 weeks
for 1,N2-εdGuo, M1dGuo,
AcrdGuo, or CrdGuo following exposure to TCDD (100 ng/kg/day), all
of them were significantly induced in animals exposed to the tertiary
mixture (TEQ 100 ng/kg/day). This oxidation DNA product data suggest
that the simple TEF methodology cannot be applied to evaluate the
diverse patterns of toxic effects induced by DLCs.