Use of polyclonal antibodies against carcinogen-DNA adducts in analysis of carcinogenesis.

Polyclonal antibodies against 3,2'-dimethyl-4-aminobiphenyl (DMAB)- and 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP)-DNA adducts were raised for their immunohistochemical demonstration in paraffin-embedded sections. Both carcinogens target multiorgans in rats with colon, mammary glands and prostate as common tumor sites. PhIP is particularly important because it is a cooked food-derived carcinogen to which man is exposed on a daily bases. Dose-related nuclear staining in various tissue of rats was observed 24 h after single applications of both carcinogens but no observable decrease in staining intensity was evident in most organs by 168 h. Staining specificity in terms of sites of tumor development was lacking. However, in target organs, semiquantitative data on adduct formation correlated with alteration in tumor response by modifying factor(s). Furthermore, human prostate tissue implanted into nude mice showed positive staining. Thus, the antibodies can be applied as tools to clarify tissue or cell-specific carcinogenesis, carcinogen-exposure levels and metabolic activation in various species, including man after tissue transplantation.