In vitro induction of benzo(a)pyrene diol epoxide-DNA adducts in peripheral lymphocytes as a susceptibility marker for human lung cancer.
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.
Li
D
D
Department of Clinical Investigations, University of Texas M.D. Anderson Cancer Center, Houston 77030, USA.
Wang
M
M
Cheng
L
L
Spitz
M R
MR
Hittelman
W N
WN
Wei
Q
Q
D015123:7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide / Q000032:analysis*; D000328:Adult; D000368:Aged; D015415:Biomarkers; D016022:Case-Control Studies; D002478:Cells, Cultured; D018736:DNA Adducts / Q000032:analysis*; D004260:DNA Repair; D004198:Disease Susceptibility; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000209:etiology*; D008214:Lymphocytes / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D012307:Risk Factors; D012907:Smoking / Q000009:adverse effects
D015415:Biomarkers; D018736:DNA Adducts; C043931:benzo(a)pyrene-7,8-dihydrodiol-9,10-epoxide-DNA; D015123:7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide