Carcinogen metabolism in human lung tissues and the effect of tobacco smoking: results from a case--control multicenter study on lung cancer patients

Environ Health Perspect. 1992 Nov:98:119-24. doi: 10.1289/ehp.9298119.


Cigarette smoking is the strongest risk factor for lung cancer, but genetically determined variations in the activities of pulmonary enzyme that metabolize tobacco-derived carcinogens may affect individual risk. To investigate whether these enzymes (e.g., CYP1A-related) can serve as markers for carcinogen-DNA damage, lung tissue specimens were taken during surgery from middle-aged men with either lung cancer or non-neoplastic lung disease. Phase I [aryl hydrocarbon hydroxylase (AHH), ethoxycoumarin O-deethylase (ECOD)] and phase II (epoxide hydrolase, UDP-glucuronosyltransferase, glutathione S-transferase) enzyme activities, glutathione and malondialdehyde contents were determined in lung parenchyma and/or bronchial tissues; some samples were also analyzed for DNA adducts, using 32P-postlabeling. The data were then analyzed for the following: a) differences in metabolic profiles between bronchial and parenchymal lung tissue; b) the effect of recent exposure to tobacco smoke on enzyme inducibility and benzo[a]pyrene metabolism; c) differences in enzyme inducibility between lung cancer and non-lung cancer patients; d) the effect of smoking on metabolism of mutagens in vitro; e) pulmonary DNA adduct levels and AHH activity in lung parenchyma of smokers and ex-smokers; f) lipid peroxidation products in lung tissue from lung cancer and non-lung cancer patients, as related to smoking habits and degree of airway obstruction; and g) prognostic value of AHH pulmonary activity in lung cancer patients. The results demonstrate a pronounced effect of tobacco smoke on pulmonary metabolism of xenobiotics and prooxidant state and suggest the existence of a metabolic phenotype at higher risk for tobacco-associated lung cancer.

Publication types

  • Comparative Study
  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • 7-Alkoxycoumarin O-Dealkylase / metabolism*
  • Adenocarcinoma / enzymology*
  • Aryl Hydrocarbon Hydroxylases / metabolism*
  • Biomarkers, Tumor / metabolism*
  • Carcinogens / metabolism*
  • Carcinoma, Non-Small-Cell Lung / enzymology*
  • Carcinoma, Squamous Cell / enzymology*
  • Case-Control Studies
  • Enzyme Induction
  • Epoxide Hydrolases / metabolism*
  • Humans
  • Lipid Peroxidation
  • Lung / enzymology
  • Lung / metabolism*
  • Lung Neoplasms / enzymology*
  • Male
  • Middle Aged
  • Prognosis
  • Smoking / metabolism*


  • Biomarkers, Tumor
  • Carcinogens
  • 7-Alkoxycoumarin O-Dealkylase
  • Aryl Hydrocarbon Hydroxylases
  • Epoxide Hydrolases