DNA hypomethylation induced by non-genotoxic carcinogens in mouse and rat colon.
The ability of non-genotoxic colon carcinogens to induce DNA hypomethylation was evaluated. Administering 0, 0.2 and 0.4 mg/kg of 5-aza-2'-deoxycytidine to female mice for 5 days resulted in a dose-related decrease in 5-methylcytosine in colon DNA. Rutin (3.0 mg/kg) and five bile acids (4.0 mg/kg) were administered in the diet to male F344 rats for 14 days. Rutin and four bile acids that promote colon cancer, deoxycholic acid, chenodeoxycholic acid, cholic acid and lithocholic acid caused DNA hypomethylation, while ursodeoxycholic acid that prevents colon cancer did not. Bromodichloromethane (BDCM) was administered to male F344 rats and B6C3F1 mice by gavage at 0, 50 and 100 mg/kg or in their drinking water at 0, 350 and 700 mg/l for up to 28 days. In rats, BDCM decreased DNA methylation, being more effective when administered by gavage, correlating to its greater carcinogenic potency by this route. In mice, BDCM did not decrease DNA methylation, corresponding to its lack of carcinogenic activity in the colon of this species. In summary, the ability of non-genotoxic colon carcinogens to cause DNA hypomethylation correlated with their carcinogenic activity in the colon.
Pereira
Michael A
MA
Department of Pathology, Medical College of Ohio, 3055 Arlington Avenue, Toledo 43614-5806, USA. pereira-1@medctr.osu.edu
Wang
Wei
W
Kramer
Paula M
PM
Tao
Lianhui
L
D000818:Animals; D001374:Azacitidine / Q000031:analogs & derivatives* / Q000494:pharmacology; D002273:Carcinogens; D002635:Chenodeoxycholic Acid; D019826:Cholic Acid; D003106:Colon / Q000187:drug effects; D003110:Colonic Neoplasms / Q000139:chemically induced* / Q000235:genetics*; D004247:DNA / Q000187:drug effects*; D019175:DNA Methylation; D000077209:Decitabine; D003840:Deoxycholic Acid; D004305:Dose-Response Relationship, Drug; D005260:Female; D008095:Lithocholic Acid; D008297:Male; D051379:Mice; D051381:Rats; D011916:Rats, Inbred F344; D012431:Rutin; D013997:Time Factors
D002273:Carcinogens; D003840:Deoxycholic Acid; D002635:Chenodeoxycholic Acid; D012431:Rutin; D008095:Lithocholic Acid; D000077209:Decitabine; D004247:DNA; D019826:Cholic Acid; D001374:Azacitidine