Induction of unscheduled DNA synthesis in rat stomach mucosa by glandular stomach carcinogens.

ABSTRACT

Induction of unscheduled DNA synthesis (UDS) (repair DNA synthesis) in stomach pyloric mucosa of the F344/- DuCrj rat was examined in in vitro organ cultures in the presence of tritiated thymidine ([3H]dThd) and hydroxyurea after administration of chemical carcinogens in vivo. The DNA fraction was extracted from the cultured tissue, and the incorporation of [3H]dThd into DNA was determined in a liquid scintillation counter. DNA concentration was determined spectrophotometrically with either diphenylamine or 3,5- diaminobenzoic acid. A good correlation between induction of UDS and site specificity of carcinogens was observed. The glandular stomach carcinogens N-methyl-N'-nitro-N-nitrosoguanidine (CAS 70-25-7), N-ethyl-N'-nitro-N-nitrosoguanidine (CAS 63885-23-4), N-propyl-N'-nitro-N-nitrosoguanidine, 4-nitroquinoline 1-oxide (CAS 56-57-5), and N-nitroso-N-methylurethane (CAS 615-53-2) induced UDS in the pyloric mucosa of the stomach. UDS could be detected 2-4 hours after administration of carcinogens in vivo by the present method. The forestomach carcinogens 1-methyl-1-nitrosourea (CAS 684-93-5) and aristolochic acid (CAS 1398-06-7) and the nongastric carcinogens 2-acetylaminofluorene (CAS 53-96-3), 3-amino-1,4-dimethyl-5H-pyrido[4,3-b]indole, 3-amino-1-methyl-5H-pyrido[4,3-b]indole, and dimethylnitrosamine (CAS 62-75-9) did not induce UDS in the pyloric mucosa.