Modulation of oxidative DNA damage by repair enzymes XRCC1 and hOGG1.
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/10(6) 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/10(6) 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/10(6) 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.
Institute for Prevention and Occupational Medicine of the German Social Accident Insurance - Institute of the Ruhr-Universität Bochum (IPA), Bochum, Germany. rihs@ipa-dguv.de
Hans-Peter
HP
Rihs
Boleslaw
B
Marczynski
Anne
A
Lotz
Monika
M
Raulf-Heimsoth
Thomas
T
Brüning
D000293:Adolescent; D000328:Adult; D000336:Aerosols; D004247:DNA / Q000235:genetics; D004249:DNA Damage; D045647:DNA Glycosylases / Q000235:genetics* / Q000502:physiology*; D004260:DNA Repair / Q000502:physiology; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000502:physiology*; D005260:Female; D005838:Genotype; D005858:Germany; D006147:Guanine / Q000031:analogs & derivatives / Q000378:metabolism; D006801:Humans; D006838:Hydrocarbons / Q000009:adverse effects*; D019570:Inhalation Exposure; D007962:Leukocytes / Q000737:chemistry; D008297:Male; D008875:Middle Aged; D016273:Occupational Exposure / Q000009:adverse effects*; D018384:Oxidative Stress / Q000502:physiology*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D012907:Smoking / Q000378:metabolism; D000076105:X-ray Repair Cross Complementing Protein 1; D055815:Young Adult
D000336:Aerosols; D004268:DNA-Binding Proteins; D006838:Hydrocarbons; D000076105:X-ray Repair Cross Complementing Protein 1; C000619371:XRCC1 protein, human; C024829:8-hydroxyguanine; D006147:Guanine; C006647:asphalt; D004247:DNA; D045647:DNA Glycosylases; C479058:oxoguanine glycosylase 1, human