EDITORIALS Molecular Dosimeters of Smoking Damage in the Lung

Traditional epidemiologic research relied on self-reported measures of “external exposure ” in defining the association be-tween cigarette smoking and cancer risk. With elucidation of carcinogen-induced genetic and epigenetic events, knowledge of the molecular etiology of smoking-related cancers has expanded rapidly and has facilitated the study of tobacco carcinogenesis. The dose of tobacco carcinogens to which lung tissue is ex-posed is modulated by genetic polymorphisms in the enzymes responsible for activation (phase I) and detoxification (phase II) of tobacco carcinogens. For example, the cytochrome(s) P450 multigene superfamily of enzymes is involved in phase I oxida-tive processes that may create intermediates that are more reac-tive than the parent compounds and can be carcinogenic or mu-tagenic. Phase II metabolic processes generally inactivate these genotoxic compounds through conjugation that promotes cellu