title: Gamma-radiation-induced single cell DNA damage as a measure of susceptibility to lung cancer: a preliminary report.
abstract: The comet assay is a sensitive and rapid method for detecting DNA single-strand and double-strand breaks and the individual cell's DNA repair profile. This pilot study was designed to determine whether the comet assay could measure inherited susceptibility to lung cancer. We applied the comet assay in the alkaline condition to test the DNA damage in gamma-irradiated and untreated cultured peripheral blood lymphocytes of 31 cases with previously untreated lung cancer and 39 controls. For each culture, 200 consecutive cells were examined and the number of cells with DNA uncoiling under electrophoresis (<comet cells>) was recorded. The comet tail length (the radius of the nucleus plus the length of the migrated DNA) at 400-fold magnification was measured for the first 50 identified comet cells. The mean number of induced comet cells was significantly higher in cases (96.0+/-45.7) than matched controls (68.9+/-35.8) (P<0.05). However, no significant difference was observed in induced comet tail length between cases and controls. When we categorized the number of comet cells by the 75th percentile value in the controls, a higher number of comet cells was associated with significantly increased risk for lung cancer [odds ratio = 4.8 (confidence intervals of 1.5, 15.2)] after adjustment for age, sex, ethnicity and smoking status. The number of gamma-irradiation-induced comet cells (r=0.499, P<0.05) and comet tail length (r=0.520, P<0.05) correlated with the results on a previously reported lung cancer susceptibility marker, bleomycin sensitivity. Also, the number of gamma-irradiation-induced comet cells correlated with the results of the benzo[alpha]pyrene diol epoxide mutagen sensitivity assay, which quantifies induced chromatid breaks (r=0.275, P<0.05). The comet assay might be a simple and inexpensive tool for detecting genetic susceptibility to lung cancer.
authors.affiliation: Department of Epidemiology, The University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Blvd., Houston, TX 77030, USA.
authors.forename: H
authors.initials: H
authors.lastname: Zhang
authors.forename: T A
authors.initials: TA
authors.lastname: Buchholz
authors.forename: D
authors.initials: D
authors.lastname: Hancock
authors.forename: M R
authors.initials: MR
authors.lastname: Spitz
authors.forename: X
authors.initials: X
authors.lastname: Wu
mesh_terms: D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D020552:Comet Assay; D016001:Confidence Intervals; D004249:DNA Damage; D005260:Female; D005720:Gamma Rays; D005820:Genetic Testing / Q000379:methods*; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics*; D008214:Lymphocytes / Q000528:radiation effects; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D010865:Pilot Projects; D012907:Smoking / Q000009:adverse effects