Oxidative DNA damage in liver of mice with different susceptibility to hepatocarcinogenesis.
Susceptibility to spontaneous or chemically-induced liver tumors in mice has been demonstrated to be strain dependent, with the tumor development or promotion phase contributing most to variability. Since reactive oxygen species are thought to play a role in carcinogenesis, especially tumor promotion, we investigated steady-state levels of 8-hydroxy-2'-deoxyguanosine (8-oxo-dG) in hepatic DNA from age matched (7 months), untreated mice of three inbred strains, that differ significantly in their susceptibility to liver carcinogenesis. Male mice of strain C3H, highly sensitive to liver tumorigenesis, had significantly higher levels of hepatic 8-oxo-dG (3.3 SE 0.2 8-oxo-dG/10(5) dG) than resistant strains C57BL (2.1 SE 0.3/10(5) dG; p < 0.01) and A/JCr (2.5 SE 0.1/10(5) dG; p < 0.015). In contrast, levels of 8-oxo-dG in livers of female A/JCr mice (3.1 SE 0.3/10(5) dG) were higher than in those of C3H (2.2 SE 0.1/10(5) dG; p < 0.025) and C57BL females (2.5 SE 0.3/10(5) dG; p = NS). Male C3H livers presented significantly more 8-oxo-dG than those of C3H females (p < 0.002). These results suggest that steady-state levels of 8-oxo-dG may contribute to the inherent differences in susceptibility to hepatocarcinogenesis in inbred strains of mice, especially the high sensitivity of C3H males.
Sipowicz
M A
MA
Laboratory of Comparative Carcinogenesis, National Cancer Institute, FCRDC, Frederick, MD 21702, USA.
Anderson
L M
LM
Kasprzak
K S
KS
D000080242:8-Hydroxy-2'-Deoxyguanosine; D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000503:physiopathology; D004247:DNA / Q000378:metabolism*; D004249:DNA Damage / Q000502:physiology*; D003849:Deoxyguanosine / Q000031:analogs & derivatives* / Q000378:metabolism*; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D008099:Liver / Q000378:metabolism*; D008113:Liver Neoplasms / Q000503:physiopathology*; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D018384:Oxidative Stress / Q000235:genetics; D012737:Sex Factors; D013045:Species Specificity
D000080242:8-Hydroxy-2'-Deoxyguanosine; D004247:DNA; D003849:Deoxyguanosine