Increased cytochrome P450 and aryl hydrocarbon receptor in bronchial epithelium of heavy smokers with non-small cell lung carcinoma carries a poor prognosis.
Smoking induces mutations via the formation of DNA-adducts in the bronchial and alveolar epithelium and contributes to the development of lung cancer. Benz(a)pyrene and nitrosamine, typical carcinogens in cigarette smoke, undergo metabolic activation by the phase I enzymes, such as cytochrome P450 (CYP) 1A1, CYP2A6 and CYP2E1. The transcriptional regulation of these phase I enzymes is regulated by arylhydrocarbon receptor (AH-R) which binds many well-known carcinogens. To identify a cause and effect relationship, the expression of cytochrome CYP and AH-R in the bronchial epithelium was correlated with the history of cigarette smoking in patients with non-small cell lung carcinoma (NSCLC). Although CYP3A+ cells were absent in the bronchial epithelium of all patients, there were many CYP2E1+ cells in heavy (>1000 cigarette/day x year) smokers (38.5%). In contra-distinction, there was significantly less number of CYP2E1+ cells in light (less than 1000 cigarette/day x year) smokers (15.6%) or non-smokers (10.0%). Similarly, there were more CYP1A1+ (19.2%) and CYP2A6+ cells in heavy (65.4%) smokers as compared to non-smokers. The number of AH-R+ cells was also significantly higher in cases with p53 mutation (62.5%) than those without (12.2%) mutation. Since in patients with early NSCLC, CYP positivity showed a close correlation with a poor survival (p less than 0.01), expression of CYP in bronchial epithelium has a prognostic potential.
Oyama
Tsunehiro
T
Department of Environmental Health, University of Occupational and Environmental Health, Yahatanishi-ku, Kitakyushu, Japan. oyama@med.uoeh-u.ac.jp
Sugio
Kenji
K
Uramoto
Hidetaka
H
Iwata
Teruo
T
Onitsuka
Takamitsu
T
Isse
Toyohi
T
Nozoe
Tadahiro
T
Kagawa
Norio
N
Yasumoto
Kosei
K
Kawamoto
Toshihiro
T
D001980:Bronchi / Q000201:enzymology / Q000378:metabolism*; D002289:Carcinoma, Non-Small-Cell Lung / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D004848:Epithelium / Q000201:enzymology / Q000378:metabolism; D016158:Genes, p53; D006801:Humans; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D009154:Mutation; D011379:Prognosis; D018336:Receptors, Aryl Hydrocarbon / Q000378:metabolism*; D012907:Smoking / Q000378:metabolism*
D018336:Receptors, Aryl Hydrocarbon; D003577:Cytochrome P-450 Enzyme System