DNA single-strand scission in the pyloric mucosa of rat stomach induced by four glandular stomach carcinogens and three other chemicals.
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. Loxtidine, an H2-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 DNA single-strand scission is a good marker for tumor-initiating activity in rat stomach mucosa.
Furihata
C
C
Department of Molecular Oncology, Institute of Medical Science, University of Tokyo, Japan. furi@ims.u-tokyo.ac.jp
Ikui
E
E
Matsushima
T
T
D015112:4-Nitroquinoline-1-oxide / Q000633:toxicity; D000097:Acetonitriles / Q000633:toxicity; D000818:Animals; D002273:Carcinogens / Q000633:toxicity*; D004249:DNA Damage; D004277:DNA, Single-Stranded / Q000187:drug effects*; D005753:Gastric Mucosa / Q000187:drug effects*; D008297:Male; D008769:Methylnitronitrosoguanidine / Q000031:analogs & derivatives / Q000633:toxicity; D009153:Mutagens / Q000633:toxicity*; D009605:Nitrosomethylurethane / Q000633:toxicity; D009853:Omeprazole / Q000633:toxicity; D011706:Pyloric Antrum / Q000187:drug effects; D051381:Rats; D011916:Rats, Inbred F344; D014230:Triazoles / Q000494:pharmacology
D000097:Acetonitriles; D002273:Carcinogens; D004277:DNA, Single-Stranded; D009153:Mutagens; D014230:Triazoles; D008769:Methylnitronitrosoguanidine; C013659:propyl-N'-nitro-N-nitrosoguanidine; C013525:ENNG; D015112:4-Nitroquinoline-1-oxide; D009605:Nitrosomethylurethane; C039993:loxtidine; C053072:1-nitrosoindole-3-acetonitrile; D009853:Omeprazole