Measurement of cytochrome P450 2A6 and 2E1 gene expression in primary human bronchial epithelial cells

Bronchogenic carcinomas arise from bronchial epithelial cells (BECs).Inhalation exposure of BECs to nitrosamines in cigarette smoke is animportant exogenous risk factor for malignant transformation of BECs. Thus,an important endogenous risk factor is likely to be the capacity of BECs tometabolize nitrosamines. Among the cytochrome P450 enzymes capable ofmetabolizing nitrosamines, CYP2A6, CYP2E1 and CYP2B6 are expressed in BECs.In this study, we used quantitative RT-PCR to evaluate expression of CYP2A6and CYP2E1 in primary human BECs from 12 non-smokers and eight smokers.CYP2A6 was expressed in 20/20 cases and quantifiable in 18/20 cases, with amean level of 580 mRNA/10(6) beta- actin mRNA. CYP2E1 expression wasobserved in 9/20 cases, but in all cases it was expressed at levels belowour limit of quantification (10 mRNA/10(6) beta-actin mRNA). There wassignificant (P < 0.05) 20-fold inter-individual variation in expressionof CYP2A6. Further, the mean level of CYP2A6 among smokers (260 mRNA/10(6)beta-actin mRNA) was significantly lower than among non-smokers (740mRNA/10(6) beta-actin mRNA). It is hypothesized that: (i) inter-individualvariation in CYP2A6 gene expression may contribute to inter-individualvariation in risk for bronchogenic carcinoma; (ii) smoking may reduce thelevel of expression of CYP2A6 in the BECs of some individuals; and (iii)CYP2A6 is more important than CYP2E1 for metabolic activation ofnitrosamines in bronchial epithelial cells.