Carcinogen metabolism in human lung tissues and the effect of tobacco smoking: results from a case--control multicenter study on lung cancer patients.
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.
Bartsch
H
H
International Agency for Research on Cancer, Lyon, France.
Petruzzelli
S
S
De Flora
S
S
Hietanen
E
E
Camus
A M
AM
Castegnaro
M
M
Alexandrov
K
K
Rojas
M
M
Saracci
R
R
Giuntini
C
C
D015660:7-Alkoxycoumarin O-Dealkylase / Q000378:metabolism*; D000230:Adenocarcinoma / Q000201:enzymology*; D001189:Aryl Hydrocarbon Hydroxylases / Q000378:metabolism*; D014408:Biomarkers, Tumor / Q000378:metabolism*; D002273:Carcinogens / Q000378:metabolism*; D002289:Carcinoma, Non-Small-Cell Lung / Q000201:enzymology*; D002294:Carcinoma, Squamous Cell / Q000201:enzymology*; D016022:Case-Control Studies; D004790:Enzyme Induction; D004851:Epoxide Hydrolases / Q000378:metabolism*; D006801:Humans; D015227:Lipid Peroxidation; D008168:Lung / Q000201:enzymology / Q000378:metabolism*; D008175:Lung Neoplasms / Q000201:enzymology*; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D012907:Smoking / Q000378:metabolism*
D014408:Biomarkers, Tumor; D002273:Carcinogens; D015660:7-Alkoxycoumarin O-Dealkylase; D001189:Aryl Hydrocarbon Hydroxylases; D004851:Epoxide Hydrolases