CYP1B1 expression in human lung

Cytochrome P450 1B1 is a recently recognized phase I bioactivating enzyme w ith high affinity for both inhaled tobacco carcinogens and 17 beta -estradi ol. We evaluated the human lung expression of this multifunctional member o f the P450 superfamily across 16 individuals. Expression of CYP1B1 was eval uated by qualitative reverse transcription-polymerase chain reaction and We stern immunoblots performed on human tumor and nontumor lung tissue. Expres sion at both mRNA and protein levels was then correlated with smoking histo ry, plasma biomarkers of tobacco exposure (nicotine and cotinine), gender, and tumor histology. CYP1B1 mRNA and protein were detected in 94 and 100% o f individuals, respectively, Multivariate analysis confirmed that there wer e more subjects dis-playing CYP1B1 mRNA expression in tumor than nontumor t issue (p = 0.0003). Correlation of CYP1B1 protein with plasma cotinine leve ls was statistically marginal (p = 0.027). Self-reported smoking history, g ender, and tumor histology did not correlate with gene expression in the mu ltivariate model. After multivariate modeling for confounding factors, the expression patterns of 5 of 16 individuals appeared to differ from the grou p as a whole for mRNA and/or protein. We conclude that CYP1B1 is commonly e xpressed in human lung and hypothesize that it may be an important phase I enzyme with respect to human lung carcinogen metabolism, warranting an unde rstanding of regulatory control and coding region polymorphisms.