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

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Abstract

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.

Original languageEnglish
Pages (from-to)4497-4503
Number of pages7
JournalFrontiers in Bioscience
Volume12
Issue number12
DOIs
Publication statusPublished - May 1 2007

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All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)

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