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 case-control 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.