Variables influencing DNA-binding in mouse liver.
The suitability of certain mouse strains for carcinogenicity testing has been questioned. Some chemicals increase the incidence of liver tumors above a relatively high background, an effect not seen in rats. This raises the question whether species and tissue specific effects are involved which are reflected in the DNA binding of metabolites. DNA binding indices in mouse liver have been determined in only a few instances. They are comparable to those found for rat liver DNA with aniline, benzo(a)-pyrene, butadiene, dimethylnitrosamine, methylnitrosourea and they are lower in the mouse with aflatoxin B1, trans-4-acetylaminostilbene and 2-aminofluorene derivatives. The available data on DNA binding in mouse liver suggest that the same adducts are formed as in rats but that metabolism and repair are variables which can modify the extent of DNA damage. However, the extent of DNA binding does not always correlate with the susceptibility of this tissue to carcinogenesis. But mouse liver is no exception in this respect. It is concluded that the formation of mouse liver tumors in long term studies with genotoxic chemicals indicates tumor initiating potential. In contrast, there are other chemicals such as chlorinated hydrocarbon insecticides which do not bind to DNA to any extent and which are not genotoxic in common short term tests and yet give rise to liver tumors in mice but not in rats. Positive results in long term studies are suggested to indicate promoting properties of such compounds.
D016604:Aflatoxin B1; D000348:Aflatoxins / Q000378:metabolism; D000818:Animals; D001555:Benzene Derivatives / Q000378:metabolism; D002273:Carcinogens / Q000378:metabolism*; D004247:DNA / Q000378:metabolism*; D004260:DNA Repair; D005449:Fluorenes / Q000378:metabolism; D008099:Liver / Q000378:metabolism*; D008114:Liver Neoplasms, Experimental / Q000139:chemically induced; D051379:Mice; D009152:Mutagenicity Tests; D051381:Rats; D013045:Species Specificity
D000348:Aflatoxins; D001555:Benzene Derivatives; D002273:Carcinogens; D005449:Fluorenes; C012177:2-aminofluorene; D004247:DNA; D016604:Aflatoxin B1