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A parallel study of in vitro sensitivity to benzo[a]pyrene diol epoxide and bleomycin in lung carcinoma cases and controls.
Cancer. 1998 Sep 15; 83(6):1118-27.C

Abstract

BACKGROUND

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.

METHODS

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.

RESULTS

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. BPDE and bleomycin sensitivity might represent different repair or sensitivity pathways; however, when these assays are used in parallel, they might refine our ability to identify high risk individuals.

Authors+Show Affiliations

Wu X
Department of Epidemiology, The University of Texas M.D. Anderson Cancer Center, Houston 77030, USA.
Gu J
No affiliation info available
Amos CI
No affiliation info available
Jiang H
No affiliation info available
Hong WK
No affiliation info available
Spitz MR
No affiliation info available

MeSH

7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxideAdultAgedAged, 80 and overBleomycinCarcinogenicity TestsCarcinogensCase-Control StudiesChromatidsChromosome AberrationsDisease SusceptibilityDose-Response Relationship, DrugFemaleHumansLung NeoplasmsLymphocytesMaleMiddle AgedTumor Cells, Cultured

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

9740076

Citation

Wu, X, et al. "A Parallel Study of in Vitro Sensitivity to Benzo[a]pyrene Diol Epoxide and Bleomycin in Lung Carcinoma Cases and Controls." Cancer, vol. 83, no. 6, 1998, pp. 1118-27.
Wu X, Gu J, Amos CI, et al. A parallel study of in vitro sensitivity to benzo[a]pyrene diol epoxide and bleomycin in lung carcinoma cases and controls. Cancer. 1998;83(6):1118-27.
Wu, X., Gu, J., Amos, C. I., Jiang, H., Hong, W. K., & Spitz, M. R. (1998). A parallel study of in vitro sensitivity to benzo[a]pyrene diol epoxide and bleomycin in lung carcinoma cases and controls. Cancer, 83(6), 1118-27.
Wu X, et al. A Parallel Study of in Vitro Sensitivity to Benzo[a]pyrene Diol Epoxide and Bleomycin in Lung Carcinoma Cases and Controls. Cancer. 1998 Sep 15;83(6):1118-27. PubMed PMID: 9740076.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - A parallel study of in vitro sensitivity to benzo[a]pyrene diol epoxide and bleomycin in lung carcinoma cases and controls. AU - Wu,X, AU - Gu,J, AU - Amos,C I, AU - Jiang,H, AU - Hong,W K, AU - Spitz,M R, PY - 1998/9/18/pubmed PY - 2000/6/20/medline PY - 1998/9/18/entrez SP - 1118 EP - 27 JF - Cancer JO - Cancer VL - 83 IS - 6 N2 - BACKGROUND: 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. METHODS: 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. RESULTS: 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. BPDE and bleomycin sensitivity might represent different repair or sensitivity pathways; however, when these assays are used in parallel, they might refine our ability to identify high risk individuals. SN - 0008-543X UR - https://www.unboundmedicine.com/medline/citation/9740076/A_parallel_study_of_in_vitro_sensitivity_to_benzo[a]pyrene_diol_epoxide_and_bleomycin_in_lung_carcinoma_cases_and_controls_ L2 - https://medlineplus.gov/lungcancer.html DB - PRIME DP - Unbound Medicine ER -