Esophageal carcinogenesis in the rat: zinc deficiency, DNA methylation and alkyltransferase activity.

Rats fed zinc-deficient diets and given an esophageal carcinogen, methylbenzylnitrosamine, develop tumors in greater incidence and with increased frequency compared to zinc-supplemented rats. This greater susceptibility is associated with a unique esophageal lesion, parakeratosis, with markedly increased epithelial necrosis and cell proliferation. Recent studies have shown that the increased susceptibility to tumorigenesis was further associated with a number of metabolic and biochemical alterations including increased binding of the carcinogen to DNA, shifts in O6-methylguanine (O6MeG)/7-methylguanine ratios and suggestions that the promutagen O6MeG lesion is not repaired effectively in the zinc-deficient esophagus; the latter was not reflected in the amount of O6-methyltransferase activity, however.

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.

The influence of dietary levels of vitamin A and fat on colon cancer.

Rats fed diets high (24%) or low (5%) in fat were given dietary levels of vitamin A (retinyl acetate) ranging from 0.3 to 30 micrograms/g food. The lowest tumor incidence was in the group fed diets high in vitamin A and low in fat.

The influence of pre- and postnatal caloric intake on colon carcinogenesis.

Mother rats were allowed to litter under conventional conditions. They were fed a complete, semipurified diet during gestation, and at time of littering the numbers of pups were reduced to either eight per litter or four per litter in two additional groups. At weaning, all rats were continued on the same diet that their mothers had consumed.

Aflatoxin-DNA adduct formation in chronically dosed rats fed a choline-deficient diet.

Nutritional modulation of male Fischer rats by a choline-deficient/methionine-low diet dramatically increases hepatocarcinogenesis and reduces time to first tumors induced by aflatoxin B1 (AFB1). The effect of this diet on hepatic aflatoxin-DNA adduct burden in male Fischer rats dosed with a carcinogenic regimen of AFB1 was examined in this study. After 3 weeks of ingestion of a choline-deficient/methionine-low diet or control semi-purified diet, rats were administered a carcinogenic regimen of 25 micrograms [3H]AFB1 for 5 days a week over 2 weeks.