Role of zinc deficiency in carcinogenesis.

Zinc is a trace element required for the growth of normal and neoplastic tissues in a variety of species. Zinc deficiency is associated with alterations in the activity of zinc-dependent enzymes essential for cell replication. Dietary zinc deficiency also increases the incidence of certain tumors while decreasing the incidence of others. The mechanism by which zinc deficiency alters carcinogenesis is not fully understood. Among those tumors whose incidence is increased by dietary zinc deficiency are carcinomas induced by dialkylnitrosamines. This class of carcinogens requires microsomal cytochrome P-450 activation to be mutagenic. Zinc deficiency is known to increase the cytochrome P-450-dependent metabolism of methylbenzylnitrosamine (MBN), an esophageal carcinogen of this class. Examination of the kinetics of this reaction reveals zinc to be a direct noncompetitive inhibitor of the microsomal metabolism of MBN. Thus the lower rate of MBN metabolism by zinc-adequate versus zinc-deficient microsomes may be due to normal tissue zinc acting as a noncompetitive inhibitor of cytochrome P-450 activity in vivo. This effect of zinc on carcinogen metabolism may explain the increased incidence of nitrosamine-induced carcinomas observed with dietary zinc deficiency.