Carcinogen-
DNA adduct levels in lung parenchyma (surgical specimens) and urothelial (exfoliated) cells of smokers, ex-smokers and non-smokers were investigated.
DNA adducts were analysed by 32P-postlabelling and levels were compared with tissue-specific activity of
cytochrome P450-related
enzymes, or whenever possible, with metabolic phenotypes and other macromolecular adducts.
Lung cancer patients who were recent smokers had significantly induced
benzo[a]pyrene (BaP)-3-hydroxylase (AHH) and
ethoxycoumarin O-deethylase activities in lung parenchyma compared with smoking non-
cancer patients. Pulmonary AHH activity showed a good correlation with the intensity of immunohistochemical staining for P4501A(1). In
lung cancer patients from Italy and Finland who were recent smokers, lung AHH activity was positively correlated (r approximately 0.65; p < 0.001) with bulky
DNA adduct levels. In some lung
DNA samples from smokers, the level of BaP-diol-
epoxide adducts determined by HPLC with fluorescence detection showed significant positive correlation with lung AHH activity and bulky
DNA adduct levels. Molecular dosimetry studies provided evidence that aromatic
amines such as
4-aminobiphenyl (ABP) in tobacco
smoke are primarily responsible for
bladder cancer in smokers. The N-(deoxyguanosin-8-yl)-4-ABP adduct was the major smoking-related adduct in
DNA of bladder biopsies from
bladder cancer patients and in the
DNA of exfoliated urothelial cells of smoking volunteers. The adduct levels of ABP with haemoglobin and with
deoxyguanosine in urothelial
DNA (determined by 32P-postlabelling) were linearly and significantly correlated, and both were related to recent cigarette smoking. Metabolic phenotype (fast/slow N-acetylator and N-oxidizer) significantly affected the levels of ABP-haemoglobin adducts.