TY - JOUR
T1 - Increased cytochrome P450 and aryl hydrocarbon receptor in bronchial epithelium of heavy smokers with non-small cell lung carcinoma carries a poor prognosis
AU - Oyama, Tsunehiro
AU - Sugio, Kenji
AU - Uramoto, Hidetaka
AU - Iwata, Teruo
AU - Onitsuka, Takamitsu
AU - Isse, Toyohi
AU - Nozoe, Tadahiro
AU - Kagawa, Norio
AU - Yasumoto, Kosei
AU - Kawamoto, Toshihiro
PY - 2007/5/1
Y1 - 2007/5/1
N2 - 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 × year) smokers (38.5%). In contra-distinction, there was significantly less number of CYP2E1+ cells in light (<1000 cigarette/day × 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 < 0.01), expression of CYP in bronchial epithelium has a prognostic potential.
AB - 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 × year) smokers (38.5%). In contra-distinction, there was significantly less number of CYP2E1+ cells in light (<1000 cigarette/day × 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 < 0.01), expression of CYP in bronchial epithelium has a prognostic potential.
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U2 - 10.2741/2404
DO - 10.2741/2404
M3 - Article
C2 - 17485391
AN - SCOPUS:34347249168
VL - 12
SP - 4497
EP - 4503
JO - Frontiers in Bioscience - Landmark
JF - Frontiers in Bioscience - Landmark
SN - 1093-9946
IS - 12
ER -