Esophageal Carcinogenesis in F344 Rats by Nitrosomethylethylamines Substituted in the Ethyl Group23

Abstract

The carcinogenic activity in male F344 rats of five nitrosomethylalkylamines related to nitrosomethylethylamine has been examined. All rats were tested by administration of controlled doses of the compounds in the drinking water. Nitrosomethylbenzylamine was the most potent carcinogen of the five, causing death of most animals with tumors of the upper gastrointestinal tract (mainly the esophagus) within 6 months after a total dose of 0.2 mmol. The remaining compounds, all of which can be considered true derivatives of nitrosomethylethylamine, were less potent than nitrosomethylbenzylamine but also induced a high incidence of tumors of the esophagus. Nitrosomethyl-2-phenylethylamine and nitrosomethylneopentylamine were of comparable potency, while nitrosomethyltrifluoroethylamine was considerably less potent, as measured by the time to death with esophageal tumors. Deuterium-labeled nitrosomethylethylamine, in which deuterium replaces hydrogen on the β-carbon atom of nitrosomethylethylamine, induced a high incidence of esophageal tumors as well as liver tumors after administration of identical doses. Reactions on the β-carbon atom of nitrosomethylethylamine might be important as well as oxidation at the α-carbon atoms in determining carcinogenic effects.