Expression of cytochromes P450 1A1 and 1B1 in human lung from smokers, non-smokers, and ex-smokers.
Cytochromes P450 1A1 and 1B1 are known to bioactivate procarcinogens such as polycyclic aromatic hydrocarbons (PAHs) found in cigarette smoke and are inducible via an Ah receptor-mediated mechanism. The aim of this study was to examine the levels of expression of CYP1A1 and CYP1B1 in samples of lung from smokers (n = 18), non-smokers (n = 7), and ex-smokers (n = 7). Using immunoglobulin preparations of highly specific polyclonal antibodies and immunoblot analysis of microsomes from lung tissues, we determined the specific content for CYP1A1 and CYP1B1. For CYP1A1, we found median expression levels of 15.5 pmol/mg microsomal protein in smokers, 6.0 pmol/mg microsomal protein in non-smokers, and 19.0 pmol/mg microsomal protein in ex-smokers. The difference in median expression levels of smokers and ex-smokers compared to non-smokers was statistically significant. For CYP1B1, we found median expression levels of 1.8 pmol/mg microsomal protein in smokers, 1.0 pmol/mg microsomal protein in non-smokers, and 4.4 pmol/mg microsomal protein in ex-smokers. The difference in median expression levels between ex-smokers and non-smokers was statistically significant. These results suggest that levels of expression of CYP1A1 and CYP1B1 protein in lung tissues from smokers and ex-smokers are quantitatively greater than in non-smokers. By immunohistochemical analysis, we demonstrated the expression of CYP1A1 and CYP1B1 in normal human alveolar type I and II cells, ciliated columnar epithelial cells lining bronchoalveolar airways, and alveolar macrophages. These results confirm that CYP1A1 is expressed in normal human lung, appears to be induced in smokers, and show interindividual variation; the similar characteristics of CYP1B1 are demonstrated.
Kim
James H
JH
Department of Environmental Health Sciences, The Johns Hopkins University School of Hygiene and Public Health, Baltimore, MD 21205, USA.
Sherman
Mark E
ME
Curriero
Frank C
FC
Guengerich
F Peter
FP
Strickland
Paul T
PT
Sutter
Thomas R
TR
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001189:Aryl Hydrocarbon Hydroxylases / Q000096:biosynthesis*; D019363:Cytochrome P-450 CYP1A1 / Q000096:biosynthesis*; D065633:Cytochrome P-450 CYP1B1; D004847:Epithelial Cells / Q000201:enzymology; D005260:Female; D006801:Humans; D015151:Immunoblotting; D007150:Immunohistochemistry; D008168:Lung / Q000201:enzymology*; D008175:Lung Neoplasms / Q000201:enzymology; D008297:Male; D008861:Microsomes / Q000201:enzymology; D008875:Middle Aged; D011650:Pulmonary Alveoli / Q000201:enzymology; D012907:Smoking / Q000378:metabolism*
D001189:Aryl Hydrocarbon Hydroxylases; C585496:CYP1B1 protein, human; D019363:Cytochrome P-450 CYP1A1; D065633:Cytochrome P-450 CYP1B1