A PARALLEL STUDY OF IN-VITRO SENSITIVITY TO BENZO[A]PYRENE DIOL EPOXIDE AND BLEOMYCIN IN LUNG-CARCINOMA CASES AND CONTROLS

BACKGROUND. Because only a fraction of smokers develop neoplastic lesi ons, host factors may affect their susceptibility to the carcinogenic effects of tobacco smoke. Benzo[a]pyrene diol epoxide (BPDE) is the me tabolic product of benzo[a]pyrene (B[a]P), a constituent of tobacco sm oke. Therefore, BPDE sensitivity may shed some light on smoking-relate d carcinogenesis. METHODS, First, differential BPDE sensitivity was te sted in five lymphoblastoid cell lines. Then sensitivity to BPDE and b leomycin (an excellent lung carcinoma risk predictor) was tested in pa rallel in the lymphocytes of 57 lung carcinoma cases and 82 controls. RESULTS. The optimal BPDE treatment duration was 24 hours. The xeroder ma 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 carci noma, 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 bet ween the quartiles of BPDE-induced breaks and lung carcinoma risk, wit h ORs of 2.39, 3.12, and 1.5.03. It is noteworthy that individuals who were sensitive to both BPDE and bleomycin had a significantly increas ed OR of 38.36. CONCLUSIONS. BPDE sensitivity may be a biologic marker to identify individuals who are susceptible to the carcinogenic effec ts of tobacco smoke. BPDE and bleomycin sensitivity might represent di fferent repair or sensitivity pathways; however, when these assays are used in parallel, they might refine our ability to identify high risk individuals. (C) 1998 American Cancer Society.