DNA single-strand scission in the pyloric mucosa of rat stomach induced by four glandular stomach carcinogens and three other chemicals

Abstract

Induction of DNA single-strand scission by four glandular stomach carcinogens and three other chemicals was studied in the pyloric mucosa of rat stomach after gastric intubation. DNA single-strand scission, as was measured by the alkaline elution method, was induced by four glandular stomach carcinogens; N-nitroso- N-methylurethane at doses of 1 and 9 mg/kg body wt, 4-nitroquinoline 1-oxide at 20 and 30 mg/kg body wt, N-ethyl- N′-nitro- N-nitrosoguanidine at 30 and 100 mg/kg body wt and N-propyl- N′-nitro- N-nitrosoguanidine at 30 and 100 mg/kg body wt. DNA single-strand scission was also induced dose-dependently by a direct acting mutagen, 1-nitrosoindole-3-acetonitrile at doses of 100, 500 and 800 mg/kg body wt. Omeprazole, a proton pump inhibitor, was equivocal in its effect in this assay at 30–500 mg/kg body wt: induction was statistically significant by Cochran-Armitage binomial trend test. Loxitidine, an H 2-receptor antagonist, did not induce DNA single-strand breaks in the pyloric mucosa at a dose of 400 mg/kg body wt. The present results together with previous information suggest that SNA single-strand scission is a good marker for tumor-initiating activity in rat stomach mucosa.