Modulation of Oxidative DNA Damage by Repair Enzymes XRCC1 and hOGG1

Abstract

The influence of DNA repair gene polymorphisms (XRCC1: Arg194Trp, Arg280His, Arg399Gln; APE1: Asp148Glu; hOGG1: Ser326Cys) on oxidative DNA damage is controversial and was investigated in 214 German workers with occupational exposure to vapors and aerosols of bitumen,compared to 87 German construction workers without exposure, who were part of the Human Bitumen Study. Genotypes were determined by real-time polymerase chain reaction (PCR), and actual smoking habits by a questionnaire and cotinine analysis. Oxidative DNA damage in white blood cells (WBC) collected pre- and postshift was measured as 8-oxodGuo adducts/10⁶ dGuo by a hjigh-performance liquid chromatography electron capture detection (HPLC-ECD) method, followed by calculation of the difference between post- and preshift values (Δ8-oxodGuo/10⁶ dGuo). The 214 bitumen exposed workers showed higher median Δ8-oxodGuo values than the 87 references. In the whole study group (n = 301) there was a trend for increasing adduct values for XRCC1 Arg(GG)399Gln(AA) during a shift, especially in nonsmokers (n = 108. Referents (n = 87) displayed a similar trend for hOGG1 Ser(CC)326Cys(GG). In contrast, XRCC1 Arg(GG)280His(AA) showed a decrease of median Δ8-oxodGuo/10⁶ dGuo values in workers with exposure to vapors and aerosols of bitumen (n = 214), especially in smokers (n = 145). XRCC1 Arg194Trp and APE1 Asp148Glu displayed no marked association with Δ8-oxodGuo levels. Data indicate that the combination of different variants in DNA damage repair enzymes may modulate the production of 8-oxoguanine adducts in WBC produced by xenobiotics during a shift.