We studied effects on [3H]thymidine incorporation into the DNA of rat esophageal epithelium measured 1 hr after the thymidine injection and expressed as cpm/^g DNA. When various doses of 8 N-nitroso compounds were injected into rats 4 hr before they were killed, the highest doses inhibited the incorporation by 65 to 82%. The dose causing 50% inhibition was 2.3 mg/kg for methyl-n-amylnitrosamine, which is a specific carcinogen for the rat esophagus, and 22 mg/kg for the esophageal noncarcinogen,

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... dimethylnitrosamine (DMN). For all 8 compounds, the dose causing 50% inhibition was positively correlated with total carcinogenic dose and with total carcinogenic dose per percentage of incidence of esophageal tumors, as taken from published experiments in which the test compounds were administered chronically p.o. Esophageal DNA radioactivity was maximal 60 to 90 min after the [3H]thymidine injection. Thymidine incorpo ration remained inhibited for 2 days after methyl-n-amylnitrosarnine (2.2 mg/kg), but 1 day after DMN (20 mg/kg) was injected and was inhibited after continuous treatment for 2 weeks with methyl-n-amylnitrosamine (2 mg/liter drinking water) or DMN (20 mg/liter). The inhibition by methyl-n-amylnitrosamine was similar in different regions of the esophagus and was reduced by pretreatment with 3-methylcholanthrene and phénobarbi tal. Thymidine incorporation, without methyl-n-amylni trosamine treatment, was inhibited by fasting and by treatment with 3-methylcholanthrene and hydroxyurea, but not with urethan. The methyl-n-amylnitrosamine-DMN difference persisted when whole esophagi or esophageal epithelia were incubated in vitro with methyl-n-amylnitros amine or DMN and [3H]thymidine. In vivo thymidine in corporation was also inhibited by methyl-n-amylnitrosa mine, but only at high doses, in the hamster esophagus, hamster trachea, and rat trachea, but not in the rat forestomach. Similar results were observed for N-nitrosopiperidine in the hamster esophagus and trachea. These results were correlated with organ-specific carcmogemcity in the esophagus but not in the trachea, since nitrosamines mainly induce trachea! tumors in the hamster.