Increased cytochrome P450 and aryl hydrocarbon receptor in bronchial epithelium of heavy smokers with non-small cell lung carcinoma carries a poor prognosis

Tsunehiro Oyama, Kenji Sugio, Hidetaka Uramoto, Teruo Iwata, Takamitsu Onitsuka, Toyohi Isse, Tadahiro Nozoe, Norio Kagawa, Kosei Yasumoto, Toshihiro Kawamoto

研究成果: Contribution to journalArticle査読

18 被引用数 (Scopus)

抄録

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.

本文言語英語
ページ(範囲)4497-4503
ページ数7
ジャーナルFrontiers in Bioscience
12
12
DOI
出版ステータス出版済み - 5 1 2007
外部発表はい

All Science Journal Classification (ASJC) codes

  • 生化学、遺伝学、分子生物学(全般)
  • 免疫学および微生物学(全般)

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