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Departments of Epidemiology [Q. W., J. G., L. C., M. L. B., H. J., M. R. S.] and Thoracic and Head and Neck Medical Oncology [W. K. H.]. The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030
Benzo(a)pyrene is considered a classic DNA-damaging carcinogen and is one of a multitude of polycyclic aromatic hydrocarbons commonly found in tobacco smoke and in the ambient environment. In this report, we describe the characteristics of chromosomal aberrations induced in vitro by activated benzo(a)pyrene diol epoxide (BPDE) in lymphocyte cultures of 172 normal individuals ages 19–95 years and present the analysis of a pilot case-control study of 33 lung cancer patients and 96 selected controls without history of cancer and frequency matched on age (50–85 years) to the cases. The BPDE-induced chromosomal aberrations were predominantly single chromatid breaks, with few isochromatid breaks or exchange figures. In the 172 normal subjects, the frequencies of both spontaneous and BPDE-induced chromatid breaks were not correlated with age, sex, ethnicity, or tobacco use. However, the frequency of BPDE-induced chromatid breaks was significantly correlated with the frequency of spontaneous chromatid breaks (r = 0.19, P < 0.05). In addition, Hispanics had significantly higher mean BPDE-induced chromatid breaks than did non-Hispanic whites (P < 0.01). From the casecontrol analyses, the frequency of BPDE-induced chromosomal aberrations was significantly higher in cases (mean, 0.67 breaks/cell) than in controls (mean, 0.41 breaks/cell; P < 0.0001). An adjusted odds ratio of 6.53 (95% confidence interval, 3.74–11.4) for lung cancer was associated with increased frequency of these chromosomal aberrations. The higher rate of BPDE-induced chromosomal aberrations may be due to inefficient DNA repair. These findings warrant additional molecular epidemiological studies. The BPDE mutagen sensitivity assay will facilitate epidemiological studies of genetic susceptibility to smoking-related cancers.
1 This research work was supported by an institutional start-up fund grant (to Q. W.) and by NIH Grants CA55769 (to M. R. S.) and U19CA68437 (to W. K. H.).
2 To whom requests for reprints should be addressed, at Department of Epidemiology, Box 189, The University of Texas M. D. Anderson Cancer Center, Houston, TX 77030. Phone: (713) 792-3020; Fax: (713) 792-0807; E-mail: qwei@request.mda.uth.tmc.edu.
Received 4/29/96. Accepted 7/ 1/96.
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