Metabolic activation and biological effects of nitrosamines in the mammalian lung

Nitrosamines and their precursors are among the most common contaminants of our environment, and many of them are highly carcinogenic. Nitrosamines are believed to require metabolic activation in the host organism, and many of them demonstrate a pronounced organ and cell type specificity. This review summarizes recent in vivo and in vitro experiments which focus on the mechanisms of nitrosamine-induced lung carcinogenesis. Currently available in vivo and in vitro data suggest that nitrosamines may be metabolized by cytochrome P-450, prostaglandin endoperoxide synthetase, or monoamine oxidases. The presence of one or the other of these enzyme systems may be partially responsible for the cell type-specific effects of this class of chemicals. Moreover, evidence in vitro suggests selective uptake of nitrosamines by cell type-specific receptors, a phenomenon which offers a more logical explanation than previously published theories for the selectivity of biological effects exerted by nitrosamines.