Differences in DNA-guanine alkylation between male Sprague-Dawley rats and Syrian hamsters following exposure to a single dose of pancreatic nitrosamine carcinogens.
N-Nitrosobis(2-oxopropyl)amine (BOP) and N-nitroso(2-hydroxypropyl)(2-oxopropyl)amine (HPOP) are potent pancreatic carcinogens for the Syrian hamster, while in rats they primarily target the esophagus and respiratory tract. Both species metabolize these carcinogens to yield methylating and 2-hydroxypropylating agents. Ratios of N7-methylguanine (N7-MeG) to N7-(2-hydroxypropyl)guanine (N7-HPG) in hepatic DNA of BOP- and HPOP-treated hamsters are 84 and 7, respectively. Similar ratios are observed in DNA of rat liver and hamster kidney, while in the lung and pancreas of both species and also in rat kidney, such ratios are significantly lower. Differences between hamsters and rats regarding the extent of DNA alkylation are observed with either BOP or HPOP. At 50 mg/kg BOP levels of N7-MeG are 3428, 1907, 457, and 260 mumol/mol of guanine in hamster liver, kidney, lung, and pancreas, respectively. In rats treated with the same dose of BOP, levels of this adduct in corresponding tissues are 4616, 451, 372, and 105 mumol/mol of guanine. HPOP like BOP alkylates kidney and pancreas DNA more extensively in hamsters than in rats while levels of N7-MeG in liver and lung DNA are similar in both species. Levels of the O6-methylguanine (O6-MeG) are 3.6 and 5.5 times greater in the DNA of hamster pancreas than in that of the rat after an injection of 50 mg/kg BOP and HPOP, respectively. Such differences suggest that initial alkylation of hamster pancreas is a critical factor in the induction of pancreatic cancer in this species by the above nitrosamines.(ABSTRACT TRUNCATED AT 250 WORDS)
Kokkinakis
D M
DM
Department of Pathology, Northwestern University Medical School, Chicago, Illinois 60611.
D000478:Alkylation; D000818:Animals; D002250:Carbon Radioisotopes; D002273:Carcinogens / Q000378:metabolism*; D002845:Chromatography; D006224:Cricetinae; D004247:DNA / Q000096:biosynthesis / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D006147:Guanine / Q000378:metabolism*; D007668:Kidney / Q000187:drug effects / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008168:Lung / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008647:Mesocricetus; D009602:Nitrosamines / Q000378:metabolism*; D010179:Pancreas / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains
D002250:Carbon Radioisotopes; D002273:Carcinogens; D009602:Nitrosamines; C012457:diisopropanolnitrosamine; D006147:Guanine; C013622:nitrosobis(2-oxopropyl)amine; C013624:N-nitroso(2-hydroxypropyl)(2-oxopropyl)amine; D004247:DNA