Role of genotoxic and nongenotoxic effects in multistage carcinogenicity of aromatic amines.

It has been demonstrated in several model systems that tumors arise in a multistage process. Carcinogenic aromatic amines are complete carcinogens, which usually produce tumors in typical target tissues without any additional treatment. The tissue specificity, however, cannot readily be explained by genotoxic effects, and the role of secondary effects is not well understood. Promotional pressure on initiated cells can be produced by endogenous factors but also by the chemical itself. Comparison of the effects on rat liver of 2-acetylaminofluorene (AAF) and trans-4-acetylaminostilbene (AAS) provides some evidence that initiating and promoting properties of these chemicals can be separated. AAS is a strong initiator in rat liver but seems to lack promoting activity; AAF is a less efficient initiator but has tumor promoting properties. The results obtained so far indicate that promoting pressure is not produced by the acute, cytotoxic effects of AAF. It is therefore concluded that nongenotoxic, possibly receptor-mediated effects are involved.