Inhibitory effect of ortho-aminoazotoluene on diethylnitrosamine-induced hepatocarcinogenesis in suckling mice. Phenomenon and possible mechanism

The modifying effect of one compound on the carcinogenicity of another in combined application is attributed usually to some changes in the carcinogen metabolism, i.e. its activation or inactivation. In this paper, when used separately, diethylnitrosamine (DENA) induced 4–6 times more neoplastic lesions in the liver of suckling mice than ortho-aminoazotoluene (OAT) did. However, after combined treatment with both carcinogens the total number of hepatic lesions was significantly lower than that in mice treated with DENA only. Similar effect was observed when OAT was administered 3 days before or 3 days after DENA injection. The observed protective effect is not mediated at a metabolic level, because OAT has no effect on metabolism of DENA in mouse liver. Our findings can be unequivocally explained by competition of the carcinogens for target protein molecules, presumably transcription factors, participating in hepatocyte differentiation, which differently interact with and are diversely impaired by different compounds.