C. Furihata et al., SINGLE-STRAND SCISSION IN THE PYLORIC MUCOSA OF RAT STOMACH INDUCED BY 4 GLANDULAR STOMACH CARCINOGENS AND 3 OTHER CHEMICALS, Mutation research. Genetic toxicology testing, 368(1), 1996, pp. 1-6
Induction of DNA single-strand scission by four glandular stomach carc
inogens end 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 gland
ular 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 s
ingle-strand scission was also induced dose-dependently by a direct ac
ting 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 sta
tistically significant by Cochran-Armitage binomial trend test. Loxtid
ine, an H-2-receptor antagonist, did not induce DNA single-strand brea
ks in the pyloric mucosa at a dose of 400 mg/kg body wt. The present r
esults together with previous information suggest that DNA single-stra
nd scission is a good marker for tumor-initiating activity in rat stom
ach mucosa.