Zinc deficiency and the development of esophageal and forestomach tumors in Sprague-Dawley rats fed precursors of N-nitroso-N-benzylmethylamine.
Nine-week-old zinc-sufficient (100 mg zinc/kg feed) and zinc-deficient (7 mg zinc/kg feed) noninbred male Sprague-Dawley rats were given free access 5 days a week to deionized drinking water containing low (0.05%) or high (0.25%) quantities of benzylmethylamine (BMA) and concurrently 0.5% NaNO2. In contrast to the action of the preformed carcinogen N-nitroso-N-benzylmethylamine, which almost invariably produced esophageal tumors, oral administration of its precursors, BMA and NaNO2, resulted in forestomach tumors as well. In both the high- and low-BMA groups given precursors for 16 weeks, the incidence of papillomas in both the esophagus and forestomach was significantly higher in the zinc-deficient than in the zinc-sufficient rats, but zinc deficiency did not significantly increase the yield of forestomach carcinomas. However, when combined high BMA and NaNO2 administration was prolonged to 37 weeks, the yield of forestomach carcinomas was significantly greater in the zinc-deficient than in the zinc-sufficient animals. Because endogenous synthesis of N-nitrosamines from ingested precursors is an important source of human exposure to these carcinogenic compounds and because dietary zinc deficiency might be operating in some areas with a high incidence of esophageal cancer, our data are of more than routine significance.
D000818:Animals; D001596:Benzylamines / Q000378:metabolism; D001711:Biotransformation; D004128:Dimethylnitrosamine / Q000031:analogs & derivatives* / Q000378:metabolism; D004938:Esophageal Neoplasms / Q000139:chemically induced* / Q000473:pathology; D008297:Male; D009573:Nitrites / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D013274:Stomach Neoplasms / Q000139:chemically induced* / Q000473:pathology; D015032:Zinc / Q000172:deficiency*
D001596:Benzylamines; D009573:Nitrites; C029991:N-methylbenzylamine; C014707:nitrosobenzylmethylamine; D015032:Zinc; D004128:Dimethylnitrosamine