ROLE OF THE LUNG IN ACCUMULATION AND METABOLISM OF XENOBIOTIC COMPOUNDS - IMPLICATIONS FOR CHEMICALLY-INDUCED TOXICITY

The mammalian lung is exposed to and affected by many airborne and blo odborne foreign compounds. This review summarizes the role of lung in accumulation and metabolism of xenobiotics, some of which are spontane ously reactive or are metabolically activated to toxic intermediates. The specific architectural arrangement of mammalian lung favors that s o-called pneumophilic drugs are filtered out of the blood and are reta ined within the tissue as shown in particular for amphetamine, chlorph entermine, amiodarone, imipramine, chlorpromazine, propranolol, local anaesthetics, and some miscellaneous therapeutics. There is strong evi dence that intrapulmonary distribution activity and regulation of drug -metabolizing enzymes in lung is distinct from liver. This review focu ses on the metabolic rate of selected compounds in lung such as 5-fluo ro-2'-deoxyuridine, local anesthetics, nicotine, benzo(a)pyrene, ipome anol, 4-methylnitrosamino-1-(3-pyridyl)-1-butanone. It is widely accep ted that the formation of radical species is a key event in the pneumo toxic mechanisms induced by bleomycin, paraquat, 3-methylindole, butyl hydroxytoluene, or nitrofurantoin. Finally, methodological approaches to assess the capacity of lung to eliminate foreign compounds as well as biochemical features of the pulmonary tissue are evaluated briefly.