CYP1B1 expression in human lung.
Cytochrome P450 1B1 is a recently recognized phase I bioactivating enzyme with high affinity for both inhaled tobacco carcinogens and 17beta-estradiol. We evaluated the human lung expression of this multifunctional member of the P450 superfamily across 16 individuals. Expression of CYP1B1 was evaluated by qualitative reverse transcription-polymerase chain reaction and Western immunoblots performed on human tumor and nontumor lung tissue. Expression at both mRNA and protein levels was then correlated with smoking history, plasma biomarkers of tobacco exposure (nicotine and cotinine), gender, and tumor histology. CYP1B1 mRNA and protein were detected in 94 and 100% of individuals, respectively. Multivariate analysis confirmed that there were more subjects displaying CYP1B1 mRNA expression in tumor than nontumor tissue (p = 0.0003). Correlation of CYP1B1 protein with plasma cotinine levels was statistically marginal (p = 0.027). Self-reported smoking history, gender, and tumor histology did not correlate with gene expression in the multivariate model. After multivariate modeling for confounding factors, the expression patterns of 5 of 16 individuals appeared to differ from the group as a whole for mRNA and/or protein. We conclude that CYP1B1 is commonly expressed in human lung and hypothesize that it may be an important phase I enzyme with respect to human lung carcinogen metabolism, warranting an understanding of regulatory control and coding region polymorphisms.
Spivack
S D
SD
Laboratory of Human Toxicology and Molecular Epidemiology, Wadsworth Center, New York State Department of Health, Albany, New York 12209-0509, USA. spivack@wadsworth.org
Hurteau
G J
GJ
Reilly
A A
AA
Aldous
K M
KM
Ding
X
X
Kaminsky
L S
LS
D001189:Aryl Hydrocarbon Hydroxylases; D001483:Base Sequence; D002289:Carcinoma, Non-Small-Cell Lung / Q000201:enzymology; D065633:Cytochrome P-450 CYP1B1; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics / Q000378:metabolism*; D017931:DNA Primers; D005260:Female; D006801:Humans; D008168:Lung / Q000201:enzymology*; D008175:Lung Neoplasms / Q000201:enzymology / Q000556:secondary; D008297:Male; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014376:Tuberculosis / Q000201:enzymology
D017931:DNA Primers; D012333:RNA, Messenger; D003577:Cytochrome P-450 Enzyme System; D001189:Aryl Hydrocarbon Hydroxylases; C585496:CYP1B1 protein, human; D065633:Cytochrome P-450 CYP1B1