Suboptimal DNA Repair Capacity Predisposes Coke-Oven Workers To Accumulate More Chromosomal Damages in Peripheral Lymphocytes

Abstract

DNA repair is an essential mechanism for cells to maintain their genomic integrity under endogenous or exogenous assault. Reduced DNA repair capacity (DRC) is associated with increased risk for several environmentally related cancers. The micronucleus in peripheral lymphocytes has been validated as a biomarker of chromosomal damage, increasing cancer risk in human populations. We hypothesized that suboptimal DRC is associated with the increase in chromosomal damage among 94 coke-oven workers and 64 noncoke-oven controls. DRC was evaluated in isolated lymphocytes by comet assay. Chromosomal damage in peripheral lymphocytes was detected by cytokinesis-block micronucleus assay. Four common coding single nucleotide polymorphisms in the XRCC1 gene were genotyped. Coke-oven workers have significantly increased urinary 1-hydroxypyrene (9.0; 6.8-11.7 microg/L versus 1.5, 1.3-1.7 microg/L; P<0.01) and micronucleus frequency (7.4 per thousand+/-4.3 per thousand versus 3.0 per thousand+/-3.0 per thousand; P<0.01), and decreased DRC (55.9%+/-16.4% versus 63.6%+/-18.5%; P<0.01) compared with controls. Significant correlations between DRC and micronucleus frequency were found in coke-oven workers (r=-0.32; P<0.01; n = 94) and all study subjects (r=-0.32; P<0.001; n=158) but not in controls (r=-0.21; P=0.11; n=64). Variants of the Arg399Gln polymorphism were associated with a decreased DRC in both coke-oven workers (51.6%+/-16.1% versus 60.6%+/-15.7%; P<0.01) and controls (59.1%+/-18.5% versus 68.4%+/-17.5%; P=0.04). The complicated interrelationship of these multiple biomarkers was also identified by path analysis. These findings should facilitate developing a biomarker-based risk assessment model for lung cancer in this occupational population.