Gastric and oesophageal carcinogenesis: models for the identification of risk and protective factors.
Male weanling rats of the Charles River Sprague-Dawley strain were exposed to N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) in the water for 3 months at the concentration of 75 ml/litre. Other real or potential risk factors were administered, alone or in combination with MNNG. When MNNG was administered in combination with NaCl, bile acids, aspirin or BHA, forestomach tumours were enhanced. MNNG-induced tumours were inhibited by selenium or by difluoromethylornithine, an ornithine decarboxylase inhibitor. BHA alone caused forestomach tumours. When BHA was administered by dietary means or by gavage, alone or in combination with MNNG, the gavage method resulted in greater tumorigenesis than dietary exposure. This increase was associated with increased [3H]thymidine labelling of forestomach epithelium and increased hyperplasia. Oesophageal carcinogenesis induced by methylbenzylnitrosamine (MBN) was enhanced by zinc deficiency, alcohol and 13-cis-retinoic acid. Zinc deficiency also resulted in oesophageal tumours in rats exposed to the hepatocarcinogen dimethylnitrosamine. Riboflavin deficiency injured oral and oesophageal epithelium and increased sensitivity to MBN-induced oesophageal tumours.
D000284:Administration, Oral; D000818:Animals; D002083:Butylated Hydroxyanisole / Q000633:toxicity*; D004128:Dimethylnitrosamine / Q000031:analogs & derivatives / Q000633:toxicity; D004347:Drug Interactions; D000518:Eflornithine / Q000627:therapeutic use; D004938:Esophageal Neoplasms / Q000139:chemically induced*; D008297:Male; D008769:Methylnitronitrosoguanidine / Q000633:toxicity*; D051381:Rats; D011919:Rats, Inbred Strains; D012643:Selenium / Q000627:therapeutic use; D013274:Stomach Neoplasms / Q000139:chemically induced* / Q000517:prevention & control; D015032:Zinc / Q000172:deficiency
D008769:Methylnitronitrosoguanidine; D002083:Butylated Hydroxyanisole; C014707:nitrosobenzylmethylamine; D012643:Selenium; D015032:Zinc; D004128:Dimethylnitrosamine; D000518:Eflornithine