SPECIES AND TISSUE SPECIFICITIES OF I-COMPOUNDS AS CONTRASTED WITH CARCINOGEN ADDUCTS IN LIVER, KIDNEY AND SKIN DNA OF SPRAGUE-DAWLEY RATS, ICR MICE AND SYRIAN-HAMSTERS

I-compounds are age-related bulky DNA modifications that are detected in untreated animals by P-32-postlabeling. To characterize their properties, I-compounds were compared with carcinogen-DNA adducts in liver, kidney and skin of three rodent species. Weanling female Sprague-Dawley rats, ICR mice and Syrian hamsters were fed Teklad LM485 chow diet for 3 months and raised concurrently and strictly under the same environmental conditions. Animals of each species were treated topically with 24 mu-mol/kg dibenz[a,j]acridine per day for 3 days, then by gavage once with a mixture of safrole and 7,12-dimethylbenz[a]anthracene (60 and 80-mu-mol/kg respectively), or with one of the individual carcinogens. Liver, kidney and skin DNA from carcinogen-exposed (24 h after treatment) and unexposed animals was analyzed by the monophosphate version of the P-32-postlabeling assay. While each of the three carcinogens produced qualitatively identical major adduct patterns in all samples examined, I-compounds in untreated animals showed distinct species- and tissue-dependent profiles. Rats displayed the highest I-compound levels but the lowest adduct levels in both liver and kidney among the three species. These findings demonstrate fundamental differences between I-compounds and carcinogen-DNA adducts, and support the hypothesis that I-compound formation is primarily related to species-specific, i.e. genetically determined, normal metabolic activities rather than exposure to environmental genotoxic carcinogens.