Given the same exposure,
DNA adduct profiles can be considered as a phenotypic marker for
carcinogen metabolism and DNA repair, which may reflect individual susceptibility to chemical
carcinogenesis. Based on this notion, we have established a straightforward assay that measures induced
DNA adducts in peripheral lymphocytes exposed in vitro to a model
carcinogen,
benzo(a)pyrene diol
epoxide (
BPDE) by 32P-postlabeling. To test the hypothesis that the levels of induced
DNA adducts are a predictor for
cancer risk, we conducted a pilot study of 21
lung cancer patients and 41 healthy frequency-matched controls. We found that the peripheral lymphocytes of
cancer patients tended to accumulate higher levels of
BPDE-DNA adducts than controls did (mean +/- SE of relative adduct labeling x 10(7) value; 59.6 +/- 12.0 versus 39.4 +/- 6.1 for cases and controls, respectively; P = 0.09). Using the tertile relative adduct labeling value of controls (10 adducts/10(7)
nucleotides) as the cutoff point, 18 of 21 cases and 23 of 41 controls distributed above this level (odds ratio, 4.7; 95% confidence interval, 1.2-18.5). In logistic regression analysis, the level of induced adduct was an independent risk factor (odds ratio, 6.4; 95% confidence interval, 1.3-29.4) after adjustment for the potential confounding factors, i.e., age, sex, ethnicity, and smoking. Stratified analyses showed that greater differences in
DNA adduct levels induced by
BPDE between cases and controls were observed in individuals younger than 65 years and in nonsmokers. Despite the small sample size, the significant association between the level of
BPDE-induced
DNA adducts and risk for
lung cancer suggests that this assay is a promising method for further investigations.