MEASUREMENT OF CYTOCHROME-P450 2A6 AND 2E1 GENE-EXPRESSION IN PRIMARYHUMAN BRONCHIAL EPITHELIAL-CELLS

Bronchogenic carcinomas arise from bronchial epithelial cells (BECs), Inhalation exposure of BECs to nitrosamines in cigarette smoke is an i mportant exogenous risk factor for malignant transformation of BECs. T hus, an important endogenous risk factor is likely to be the capacity of BECs to metabolize nitrosamines, Among the cytochrome P450 enzymes capable of metabolizing nitrosamines, CYP2A6, CYP2E1 and CYP2B6 are ex pressed in BECs, In this study, we used quantitative RT-PCR to evaluat e expression of CYP2A6 and CYP2E1 in primary human BECs from 12 non-sm okers and eight smokers. CYP2A6 was expressed in 20/20 cases and quant ifiable in 18/20 cases, with a mean level of 580 mRNA/10(6) beta-actin mRNA, CYP2E1 expression was observed in 9/20 cases, but in all cases it was expressed at levels below our limit of quantification (10 mRNA/ 10(6) beta-actin mRNA), There was significant (P < 0.05) 20-fold inter -individual variation in expression of CYP2A6, Further, the mean level of CYP2A6 among smokers (260 mRNA/10(6) beta-actin mRNA) was signific antly lower than among non-smokers (740 mRNA/10(6) beta-actin mRNA). I t is hypothesized that: (i) inter-individual variation in CYP2A6 gene expression may contribute to inter-individual variation in risk for br onchogenic carcinoma; (ii) smoking may reduce the level of expression of CYP2A6 in the BECs of some individuals; and (iii) CYP2A6 is more im portant than CYP2E1 for metabolic activation of nitrosamines in bronch ial epithelial cells.