Induction of Mouse Lung Adenomas by Amines or Ureas Plus Nitrite and by N-Nitroso Compounds: Effect of Ascorbate, Gallic Acid, Thiocyanate, and Caffeine2

Abstract

Lung adenomas were induced in strain A mice by chronic treatment with N-nitroso compounds (given in drinking water) and with amines or ureas in food plus NaNO₂ in drinking water. We studied the effects of varying the concentrations of three N-nitroso compounds and NaNO₂ concentration in the morpholine plus NaNO₂ and methylurea plus NaNO₂ systems. Sodium ascorbate (NaASC) at the highest level tested (11.5 or 23 g/kg food) gave 89–98% inhibition of adenoma induction by the NaNO₂ plus piperazine, morpholine, and methylurea systems. In 7 groups, NaASC produced increases of 15–59% in adenoma induction by nitrosomorpholine (NM) and mononitrosopiperazine (MNP), possibly because the mice consumed more of the nitrosamine solution. Adenoma induction by morpholine plus NaNO₂ was strongly inhibited by gallic acid, moderately inhibited by caffeine, and unaffected by thiocyanate (all added to the food). Gallic acid inhibited or had no effect on the action of NM and MNP. We discussed the proposal that NaASC (or perhaps gallic acid) be administered with readily nitrosatable drugs.