{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,3]],"date-time":"2025-12-03T17:10:10Z","timestamp":1764781810209},"reference-count":39,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2008,7,14]],"date-time":"2008-07-14T00:00:00Z","timestamp":1215993600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Environ and Mol Mutagen"],"published-print":{"date-parts":[[2008,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>We have applied the alkaline comet assay to study the functional impact of gene polymorphisms in base excision repair (<jats:italic>APEX1<\/jats:italic> Asp148Glu, <jats:italic>XRCC1<\/jats:italic> Arg194Trp, <jats:italic>XRCC1<\/jats:italic> Arg399Gln) and homologous recombination repair (<jats:italic>XRCC3<\/jats:italic> Thr241Met, <jats:italic>NBS1<\/jats:italic> Glu185Gln), two pathways that play crucial roles in the repair of DNA damage induced by methylmethane sulphonate (MMS). We also examined the effect of polymorphisms in mismatch repair (<jats:italic>MLH1<\/jats:italic> \u221293 A\/G) and nucleotide excision repair (<jats:italic>XPD<\/jats:italic> Lys751Gln) as putative negative controls based on the limited roles of these pathways in MMS\u2010induced repair. Phytohemagglutinin\u2010stimulated peripheral lymphocytes from 52 healthy individuals were treated with MMS and allowed to repair for 0, 15, 40, or 120 min after a 6\u2010min washing step. DNA damage was measured as a pseudo\u2010percentage score (comparable to % tail DNA) converted from a total visual score calculated from the distribution of cells with different degrees of damage (normal, mild, moderate and severe). The repair was faster at the beginning of the observation period than towards the end, and was not complete after 2 hr. Presence of the <jats:italic>APEX1<\/jats:italic> 148Asp, <jats:italic>XRCC3<\/jats:italic> 241Met or <jats:italic>NBS1<\/jats:italic> 185Gln alleles were significantly associated with a high pseudo\u2010percentage score (above median) at early time points, with the <jats:italic>APEX1<\/jats:italic> effect being most prolonged (up to 40 min after washing, odds ratio 5.6, 95% confidence interval 2.0\u201315.5). No significant effects were seen with the <jats:italic>XRCC1<\/jats:italic> Arg194Trp, <jats:italic>XRCC1<\/jats:italic> Arg399Gln, <jats:italic>MLH1<\/jats:italic> \u221293A\/G and <jats:italic>XPD<\/jats:italic> Lys751Gln polymorphisms. Our results provide evidence for the functional nature of the variant alleles studied in the <jats:italic>APEX1, XRCC3,<\/jats:italic> and <jats:italic>NBS1<\/jats:italic> genes. Environ. Mol. Mutagen., 2008. \u00a9 2008 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/em.20415","type":"journal-article","created":{"date-parts":[[2008,7,14]],"date-time":"2008-07-14T19:26:26Z","timestamp":1216063586000},"page":"669-675","source":"Crossref","is-referenced-by-count":6,"title":["Influence of DNA repair gene polymorphisms on the initial repair of MMS\u2010induced DNA damage in human lymphocytes as measured by the alkaline comet assay"],"prefix":"10.1002","volume":"49","author":[{"given":"Charlotta","family":"Ryk","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael N.","family":"Routledge","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"James M.","family":"Allan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christopher 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