Dietary hydrogen peroxide enhances hepatocarcinogenesis in trout: correlation with 8-hydroxy-2'-deoxyguanosine levels in liver DNA.
The tumor-enhancing effect of hydrogen peroxide (H2O2) in N-methyl-N'-nitro-N-nitrosoguanidine (MNNG)-initiated rainbow trout hepatocarcinogenesis was investigated and correlated with the levels of the mutagenic DNA adduct 8-hydroxy-2'-deoxyguanosine (oh8dG). In addition, the protective role of vitamin E was examined in relation to tumor enhancement and oh8dG levels in liver DNA. Trout were fed diets containing two levels of vitamin E (1000 or 20 mg/kg wet wt), each of which were made up to contain three levels of H2O2 (0, 600 or 3000 p.p.m.). Dietary vitamin E levels had no significant effect on tumor incidence or levels of oh8dG in liver DNA. On the other hand, dietary H2O2 enhanced liver tumors in a dose-dependent manner. Liver tumor incidence correlated significantly with the mean level of liver DNA oh8dG content (r = 0.87). We conclude that the H2O2 tumor-enhancing effect coincides with higher levels of oh8dG in the trout liver genome. Thus, rainbow trout may be a useful model for the study of the relationship of oh8dG levels in vivo to enhancement or promotion of carcinogenesis and its modulation by dietary enhancers and inhibitors of oxidative stress.
Kelly
J D
JD
Marine/Freshwater Biomedical Center, Oregon State University, Corvalis 97331-6602.
Orner
G A
GA
Hendricks
J D
JD
Williams
D E
DE
D000080242:8-Hydroxy-2'-Deoxyguanosine; D000818:Animals; D002273:Carcinogens / Q000633:toxicity*; D004247:DNA / Q000378:metabolism*; D003849:Deoxyguanosine / Q000031:analogs & derivatives* / Q000378:metabolism; D004032:Diet; D006861:Hydrogen Peroxide / Q000633:toxicity*; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008114:Liver Neoplasms, Experimental / Q000139:chemically induced* / Q000517:prevention & control; D008769:Methylnitronitrosoguanidine / Q000633:toxicity; D014337:Trout; D014810:Vitamin E / Q000008:administration & dosage / Q000494:pharmacology
D002273:Carcinogens; D008769:Methylnitronitrosoguanidine; D014810:Vitamin E; D000080242:8-Hydroxy-2'-Deoxyguanosine; D004247:DNA; D006861:Hydrogen Peroxide; D003849:Deoxyguanosine