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 32P-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 mumol/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 mumol/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 32P-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.
Li
D H
DH
Department of Pharmacology, Baylor College of Medicine, Houston, TX 77030.
Xu
D C
DC
Randerath
K
K
D015127:9,10-Dimethyl-1,2-benzanthracene / Q000494:pharmacology; D000166:Acridines / Q000494:pharmacology; D000367:Age Factors; D000818:Animals; D002273:Carcinogens / Q000494:pharmacology; D006224:Cricetinae; D004247:DNA / Q000737:chemistry*; D005260:Female; D007668:Kidney / Q000737:chemistry*; D008099:Liver / Q000737:chemistry*; D009928:Organ Specificity; D051381:Rats; D011919:Rats, Inbred Strains; D012451:Safrole / Q000494:pharmacology; D012867:Skin / Q000737:chemistry*; D013045:Species Specificity
D000166:Acridines; D002273:Carcinogens; C022289:dibenzacridine; D015127:9,10-Dimethyl-1,2-benzanthracene; D004247:DNA; D012451:Safrole