ANALYSIS OF CYP2D6 EXPRESSION IN HUMAN LUNG - IMPLICATIONS FOR THE ASSOCIATION BETWEEN CYP2D6 ACTIVITY AND SUSCEPTIBILITY TO LUNG-CANCER

We have studied whether CYP2D6 is expressed in human lung tissue, usin g a specific and sensitive reverse transcriptase-polymerase chain reac tion method and immunohistochemistry. Seven out of the eight patients were extensive metabolizers as shown by genotyping for the CYP2D6 (deb risoquine-sparteine) polymorphism. To investigate whether expression o f CYP2D6 in lung tumours is different horn that in normal lung tissue, tumour tissue samples were also obtained from the same eight patients , Correctly spliced CYP2D6 mRNA was detected by RT-PCR analysis in hum an liver and duodenum but not in any of the lung samples, In accordanc e with these negative results, immunoreactivity for CYP2D6 protein, us ing specific monoclonal and polyclonal antibodies, was very low or abs ent, No specific cell type of lung tissue showed strong immunoreactivi ty for CYP2D6, although expression of CYP3A could be clearly demonstra ted in the same tissue samples, Moreover, a Western blot analysis reve aled no signal in lung microsomes from two additional extensive metabo lizers. Taken together, these results indicate that expression of CYP2 D6 in human lung is absent or very low These findings thus argue again st a significant local metabolic activation of procarcinogenic agents by CYP2D6 in the lung.