A wide variety of chemical compounds are capable of causing tumor formation in mammals. Some of these compounds become genotoxic by forming covalent modifications of DNA either directly or through reactive metabolites. The formation of these DNA adducts is considered to be a common mechanism by which structurally diverse chemicals ultimately produce mutations and cancer. The 32p- postlabeling method is a sensitive technique whereby lipophilic or bulky adducts, such as those derived by exposure to polycyclic aromatic hydrocarbons can be detected in preparations of DNA. We have previously shown that multiple adducts are visualized on thin-layer maps when human lymphocyte DNA is analyzed by the 32p- postlabeling method. Using the P1- nuclease-modification of this method, we found a range of one adduct per 10(7)-10(8) nucleotides for the subjects studied and that each individual had a unique adduct profile. During the latest period covered, we focused on refining the method with regard to improving sensitivity and chromatographic consistency. The modifications are being applied in two separate studies. In one investigation, we are evaluating whether pregnancy/lactation provides a permanent influence on the capacity of the mouse mammary gland to repair DNA adducts produced by treatment with benzo(a] pyrene. In another study, we are evaluating 32P-postlabeling thin-layer maps of kidney DNA obtained from hamsters treated with various estrogens known to induce tumor formation in this organ.
