DNA Adduct Formation During Chronic Administration of an Aromatic Amine

Abstract

DNA adduct formation is considered to play an integral part in the initiation of tumors. Since most human exposure to chemical carcinogens is chronic, it is important to investigate DNA adduct formation in relation to preneoplasia and tumorigenesis in animal models using a similar type of exposure. In this communication, two different experimental systems are described in which rodents were continuously fed 2-acetylaminofluorene (AAF). In both experiments, DNA adducts were detected with antisera specific for the acetylated [N-(deoxyguanosin-8-уl)-2-acetylaminofluorene; dG-C8-AAF] and deacetylated [N-(deoxyguanosin-8-y1)-2-aminofluorene; dG-C8-AF] C8-substituted deoxyguanosine adducts of AAF. The first study compared the tumor incidence in the livers and bladders of mice chronically fed seven different doses of AAF for up to 33 months with the DNA adducts in these tissues after one month of feeding AAF at similar doses. In the second investigation, four different hepatocarcinogenesis protocols were used to induce enzyme-altered, preneoplastic foci in the livers of rats. The animals were then fed AAF for five to six days and the concentration of AAF-DNA adducts was determined in the foci and adjacent tissues. Taken together, these studies suggest that initiating events involving DNA adducts occur relatively early in the carcinogenic process, and that cells progressing to form tumors may not necessarily contain or be able to form DNA adducts. Furthermore, the number of adduct-related events required for tumor initiation appears to differ among tissues of the same animal.