Because only a fraction of smokers develop neoplastic lesions, host factors may affect their susceptibility to the carcinogenic effects of tobacco smoke.
Benzo[a]pyrene diol epoxide (BPDE) is the metabolic product of benzo[a]pyrene (B[a]P), a constituent of tobacco smoke.
Therefore, BPDE sensitivity may shed some light on smoking-related carcinogenesis.
First, differential BPDE sensitivity was tested in five lymphoblastoid cell lines.
Then sensitivity to BPDE and bleomycin (an excellent lung carcinoma risk predictor) was tested in parallel in the lymphocytes of 57 lung carcinoma cases and 82 controls.
The optimal BPDE treatment duration was 24 hours.
The xeroderma pigmentosum cell line was the most sensitive, followed by head and neck cancer, ataxia telangiectasia, and normal cells.
The mean breaks per cell for cases and controls were 0.78 and 0.46, respectively (P<0.0001).
BPDE sensitivity was significantly associated with lung carcinoma, with an odds ratio (OR) of 7.26, compared with an OR of 4.56 for bleomycin sensitivity.
There was also a dose-response correlation between the quartiles of BPDE-induced breaks and lung carcinoma risk, with ORs of 2.39,3.12, and 15.03.
It is noteworthy that individuals who were sensitive to both BPDE and bleomycin had a significantly increased OR of 38.36.
CONCLUSIONS, BPDE sensitivity may be a biologic marker to identify individuals who are susceptible to the carcinogenic effects of tobacco smoke. (...)
Mots-clés Pascal : Carcinome, Bronchopulmonaire, Facteur risque, Epidémiologie moléculaire, Test mutagénicité, Benzo pyrène, Epoxyde, Métabolite, Bléomycine, Cytogénétique, In vitro, Carcinogenèse, Tabagisme, Etats Unis, Amérique du Nord, Amérique, Homme, Appareil respiratoire pathologie, Poumon pathologie, Bronche pathologie, Tumeur maligne, Génétique
Mots-clés Pascal anglais : Carcinoma, Bronchopulmonary, Risk factor, Molecular epidemiology, Mutagenicity testing, Benzopyrene, Epoxide, Metabolite, Bleomycin, Cytogenetics, In vitro, Carcinogenesis, Tobacco smoking, United States, North America, America, Human, Respiratory disease, Lung disease, Bronchus disease, Malignant tumor, Genetics
Notice produite par :
Inist-CNRS - Institut de l'Information Scientifique et Technique
Cote : 98-0429594
Code Inist : 002B11A. Création : 25/01/1999.