TY - JOUR
T1 - 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
AU - Li, Donghui
AU - Xu, Decheng
AU - Randerath, Kurt
N1 - Funding Information:
We thank Dr E.Randerath for discussion and suggestions. D.Lin provided assistance in animal feeding and other experiments. This work was made possible by grants from the National Cancer Institute (R37 CA32157), the National Institute on Aging (R01 AG07750) and the National Institute of Environmental Health Sciences (P42 ES04917).
PY - 1990/12
Y1 - 1990/12
N2 - 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 Tekiad 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 μmol/kg dibenz [α,j]acridine per day for 3 days, then by gavage once with a mixture of safrole and 7,12-dlmethylbenz[α]anthracene (60 and 80 μmol/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 carcino gen-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.
AB - 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 Tekiad 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 μmol/kg dibenz [α,j]acridine per day for 3 days, then by gavage once with a mixture of safrole and 7,12-dlmethylbenz[α]anthracene (60 and 80 μmol/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 carcino gen-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.
UR - http://www.scopus.com/inward/record.url?scp=0025634165&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0025634165&partnerID=8YFLogxK
U2 - 10.1093/carcin/11.12.2227
DO - 10.1093/carcin/11.12.2227
M3 - Article
C2 - 2124953
AN - SCOPUS:0025634165
SN - 0143-3334
VL - 11
SP - 2227
EP - 2232
JO - Carcinogenesis
JF - Carcinogenesis
IS - 12
ER -