The role of DNA damage in chemical carcinogenesis of aromatic amines.

Many findings support the notion that the generation of DNA adducts by aromatic amines is causally related to carcinogenesis. Adducts have been identified in most cases and representative examples are reviewed. However, extent and persistence of DNA adducts (DNA dose) does not correlate satisfactorily with the tumor response of different tissues. Distribution of DNA damage, repair, indirect and secondary DNA damage are discussed as possible explanations for the observed noncorrelations. In addition, however, it is proposed to pay attention to specific mechanisms such as receptor mediated cellular effects which are not related to the generation of electrophiles. The effects of trans-4-aminostilbene and 2-amino-fluorene derivatives on rat liver are compared. It is concluded that trans-4-acetylamino-stilbene is a strong liver tumor initiator but an incomplete liver carcinogen lacking tumor promoting properties, and that 2-acetylaminofluorene is a complete liver carcinogen with initiating and promoting properties.