DNA ADDUCT FORMATION AND TUMORIGENESIS IN MICE DURING THE CHRONIC ADMINISTRATION OF 4-AMINOBIPHENYL AT MULTIPLE-DOSE LEVELS

Recent studies have demonstrated the presence of DNA adducts from 4-am inobiphenyl (4-ABP) in the bladder cells of humans; however, the corre lation between the concentration of these adducts and the tumorigenic response is not clear, To help elucidate this relationship, we have in vestigated DNA adduct formation in experimental animals continuously a dministered 4-ABP, Male and female BALB/c mice were treated for 28 day s with 4-ABP hydrochloride in their drinking water, DNA adducts in tar get tissues (liver of females and bladder of males) were identified an d quantified by P-32-postlabeling analyses and radioimmunoassays, Thes e results were compared to previously reported tumor incidences obtain ed from the lifetime administration of 4-ABP hydrochloride, The major adduct observed in both tissues was N-(deoxyguanosin-8-yl)-4-ABP, In t he bladders of both sexes and the livers of female mice, adduct levels increased with dose at low doses, but saturation was observed at high doses. In the livers of males, the adduct levels were linearly correl ated with dose throughout the entire dose range, A comparison between DNA adducts and tumorigenesis indicated a linear correlation between a dduct levels and the incidence of liver tumors in female mice, In the bladders of male mice, however, the relationship was markedly nonlinea r, These data suggest that adduct formation alone is insufficient for tumorigenesis in the bladder and that other factors such as cell proli feration are necessary for tumor production.