DNA adducts in target and nontarget tissues of 3,2'-dimethyl-4-aminobiphenyl in rats

Abstract

3,2'-Dimethyl-4-aminobiphenyl (DMAB) is a potent carcinogenic aromatic amine which demonstrates multiorgan tropism in rats. Using polyclonal antibodies against DMAB-DNA adducts, an immunohistochemical procedure as well as an ELISA were applied to investigate the relationship between DMAB-DNA adduct formation and tumorigenicity. Dose-related nuclear staining was observed 24 hr after application of the carcinogen but specificity in terms of sites of tumor development was lacking. No observable decrease in staining intensity was evident in most organs by 168 hr after administration of DMAB. Specific DNA lesions which could be responsible for carcinogenesis were not detected by the 32P-postlabeling method. The tumorigenic response of the ventral prostate in five strains of rats was roughly paralleled by DMAB-DNA adduct levels generated in the tissue. Strong enhancement of bladder tumor development by combined administration of the antioxidants, butylated hydroxyanisole, or butylated hydroxytoluene, with DMAB, was well correlated with an increase in DNA adducts. Our findings so far suggest that DNA adduct formation itself does not determine the carcinogenic organotropism of DMAB. Other factors (including cell proliferation and promotion by exogenous agents) may play important additional roles. For individual target organs or tissues, however, there seems to be a correlation between adduct levels and carcinogenic potential.