Aryl hydrocarbon hydroxylase activity in pulmonary macrophages and lymphocytes from lung cancer and noncancer patients.

Cigarette smoking is epidomiologically related to lung cancer (17, 33-35), but'the mechanisms involved in the production of these carcinomas have not been delineated. One hypothesis is that malignant transformation may be initiated by exposure of the bronchial epithelium to aro matic polycyclic hydrocarbons such as BP4 and BA (which are present in cigarette smoke and are capable of inducing malignant tumors in laboratory animals) (2, 3, 20, 23). The enzyme system that metabolizes polycyclic aromatic hydrocarbons in tissues is AHH, an inducible monooxygen ase complex localized in the endoplasmic reticulum of many tissues in the body (6, 24, 25, 27). By hydmoxylation, AHH transforms polycyclic aromatic hydrocarbons into more hydnophilic products, which are usually less carcino genic. During this process, opoxides, which may be mono potent carcinogens than are their parent hydrocarbons, are transiently produced as initial intermediate products (9, 13— 16, 27, 29). The diol-epoxide, an even more reactive inter mediate that may be the proximal carcinogenic hydnocam bon, is also formed through the memetabolism of initial hydroxylated dihydnodiols (32, 39). In addition, many of the primary AHH metabolites may be memetabolized by this same monooxygenase complex to compounds with en hanced cancinogenicity (39). By generating increased quan titios of epoxides and/on diol-epoxides and by remetaboliz ing initial metabolites, high levels of AHH may be detnimen tal. Individual differences in the rate of hydmoxylation of poly cyclic hydrocarbons could be a factor in determining sus coptibility to cancinogenesis by these agents. Themeis evi donce that AHH inducibility may be genetically determined in laboratory animals and man (12, 21, 26, 36). Higher levels