Esophageal carcinogenesis in the rat: zinc deficiency and alcohol effects on tumor induction

Sprague-Dawley male rats were fed zinc-deficient or supplemented diets for 2 weeks, administered a carcinogenic dose of methylbenzylnitrosamine and observed over 20 or more weeks for effects of superimposing excess zinc or alcohol on development of esophageal tumors. In three separate experiments it was shown that (1) excess zinc offered no protection, (2) switching diets during or after carcinogen exposure pointed toward involvement of zinc in both initiation and promotion, (3) neither ethanol nor 3-methyl butanol alone affected tumorigenesis but the two combined and superimposed on a zinc deficiency resulted in a significant enhancement of neoplasia. In one group of rats fed the zinc-deficient diet only, with no carcinogen, 4 rats developed neoplasms, one of which was malignant. Cell proliferation, an integral component of zinc deficiency, appears to be an important contribution to tumor induction in this model.