Variability in the expression of enzymes metabolizing carcinogens derived from cigarette smoke may contribute to individual susceptibility to pulmonary carcinogenesis. This study was designed to determine the effects of smoking and 3 major cytochrome P450 (CYP) enzymes, i.e., CYP1A1, CYP1B1 and CYP3A, which metabolize polycyclic aromatic hydrocarbons (PAH) on PAH‐DNA adduct formation in the bronchoalveolar macrophages (BAM) of 31 smokers and 16 non‐smokers. CYP protein levels were determined by immunoblotting and PAH‐DNA adduct levels by the nuclease P1 enhanced 32P‐postlabeling method. The expression of specific CYP forms was confirmed by reverse transcriptase‐polymerase chain reaction (RT‐PCR) from 10 additional samples. CYP3A protein, CYP3A5 by RT‐PCR, was detected in the majority of samples from smokers and non‐smokers. The levels of CYP3A appeared to be lower in active smokers than in ex‐smokers (p = 0.10) or never smokers (p = 0.02). CYP1A1 was not detectable by either immunoblotting or RT‐PCR. The expression of CYP1B1 was low or undetectable in most samples. The PAH‐DNA adduct levels were higher (mean 1.57/108 nucleotides) in samples from smokers compared with non‐smokers (mean 0.42/108 nucleotides, p < 0.001) and the number of adducts correlated with the number of cigarettes smoked daily (regression analysis, p < 0.001). Higher levels of adducts were detected in samples from smokers with a high level of CYP3A compared with those with a low level (regression analysis, p = 0.002). As CYP3A5 is abundant in both lung epithelial cells and BAM, its association with adduct formation suggests that this CYP form may be important in the activation of cigarette smoke procarcinogens. Int. J. Cancer 86:610–616, 2000. © 2000 Wiley‐Liss, Inc.

The effects of smoking and DNA adduct formation were analysed in isolated human white blood cell populations. As the white cells are composed mainly of granulocytes with a short half-life and T-lymphocytes with a half-life of several years, we isolated the lymphocytes and granulocytes of 11 smokers and 10 nonsmokers to determine any smoking-related DNA adducts by the nuclease-P1-enhanced 32P-postlabelling assay. The differences between the mean lymphocyte DNA adducts/10(8) nucleotides of 31 +/- 5.7 (SE) of smokers were significantly higher (P less than 0.05) than those in the lymphocytes 13 +/- 1.6 (SE) of nonsmokers. The total DNA adducts/10(8) nucleotides obtained from the granulocytes of smokers and nonsmokers was 9.6 +/- 1.9 and 7.6 +/- 1.9 respectively. The plasma cotinine concentrations were in good agreement with the smoking information given by the individual smokers (r = 0.847, P less than 0.001). The DNA adduct levels of the lymphocytes of the 10 smokers correlated with the plasma cotinine concentrations (r = 0.639, P less than 0.05). The variation between the results was explained by the variation among the individuals and the samples, but not by the variation in the parallel determinations. More detailed studies are needed to analyse the source of the individual variations between the smokers' adduct levels, DNA repair, and differences in the metabolism of the compounds in cigarette smoke.

The urinary hydroxy-metabolites of naphthalene, phenanthrene and pyrene showed low exposure to diesel-derived PAHs; however, it was higher in exposed workers than in control group. Urinary PAH monohydroxy-metabolites measured in this study did not correlate with the PAHs in the air samples, reported earlier, in 2002 and 2003.

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Levels of aromatic DNA adducts in foundry workers and controls were followed at four annual samplings. During this time exposure to polycyclic aromatic hydrocarbons (PAH) decreased and the level of DNA adducts decreased accordingly. In the total group exposure was related to the level of adducts. Adduct levels correlated with urinary 1-hydroxypyrene (LOGU1OH), air benzo[a]pyrene, weekly working hours and daily cigarette consumption. In a multivariate model 1-hydroxypyrene had a consistent effect. Neither glutathione transferase M1 (GSTM1) nor cytochrome P450 1A1 (CYP1A1) genotypes had clear effects. Yet the individuals lacking GSTM1 had a stronger effect of LOGU1OH and some effect by other sources of PAH, such as charcoal broiled food, although all these variables were not significant in the multivariate model. The rare individuals with a CYP1A1 polymorphism MspI containing an amino acid change at isoleucine had an increased level of adducts. The results showed that the postlabelling method used was able to detect an increase in aromatic DNA adducts in leukocytes when exposure to benzo[a]pyrene in air was approximately 5 ng/m3. At such low levels smoking and charcoal broiled food may be important contributors to adducts.