ABILITY OF N-METHYL-N'-NITRO-N-NITROSOGUANIDINE, 4-NITROQUINOLINE 1-OXIDE, DIMETHYLNITROSAMINE, AND NACL TO INDUCE UNSCHEDULED DNA-SYNTHESIS, STIMULATE REPLICATIVE DNA-SYNTHESIS, AND PRODUCE DNA SINGLE-STRAND BREAKS IN PYLORIC MUCOSA OF RAT STOMACH

Male F344 rats were given test chemicals orally, and samples of their pyloric mucosa were incubated in vitro. Induction of unscheduled DNA s ynthesis (UDS) and stimulation of replicative DNA synthesis in the pyl oric mucosa were then examined by addition of [H-3]thymidine and simul taneous determinations of DNA synthesis in the presence and absence of hydroxyurea, an inhibitor of replicative DNA synthesis. DNA damage wa s also examined by the alkaline elution method with DNA single-strand scission as a marker. The results showed four types of abilities of th e chemicals to affect UDS and replicative DNA synthesis in the pyloric mucosa of rat stomach 1-2 h after their administration: (1) induction of UDS and stimulation of replicative DNA synthesis by N-methyl-N'-ni tro-N-nitrosoguanidine (MNNG), a glandular stomach carcinogen, (2) ind uction of only UDS by 4-nitroquinoline 1-oxide (4NQO), a glandular sto mach carcinogen, (3) stimulation of only replicative DNA synthesis by NaCl, a glandular stomach tumor promoter, and (4) neither induction of UDS nor stimulation of replicative DNA synthesis by dimethylnitrosami ne (DMN), a liver carcinogen. DNA single-strand scission was induced b y MNNG and 4NQO, being maximal 2 h after their administration, but was not induced by NaCl or DMN. Thus it correlated well with the inductio n of UDS. The present results indicate four types of inductive abiliti es of chemicals on UDS and replicative DNA synthesis in rat stomach py loric mucosa and show that this method can detect differences in the a ction mechanisms and organ specificities of glandular stomach carcinog ens.