{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,1]],"date-time":"2025-11-01T09:21:30Z","timestamp":1761988890415},"reference-count":36,"publisher":"Hindawi Limited","license":[{"start":{"date-parts":[[2015,1,1]],"date-time":"2015-01-01T00:00:00Z","timestamp":1420070400000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/3.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Oxidative Medicine and Cellular Longevity"],"published-print":{"date-parts":[[2015]]},"abstract":"<jats:p>We have developed a kinetic model to investigate how DNA repair processes and scavengers of reactive oxygen species (ROS) can affect the dose-response shape of prooxidant induced DNA damage. We used as an example chemical<mml:math xmlns:mml=\"http:\/\/www.w3.org\/1998\/Math\/MathML\" id=\"M1\"><mml:mrow><mml:msub><mml:mrow><mml:mtext>KBrO<\/mml:mtext><\/mml:mrow><mml:mrow><mml:mtext>3<\/mml:mtext><\/mml:mrow><\/mml:msub><\/mml:mrow><\/mml:math>which is activated by glutathione and forms reactive intermediates that directly interact with DNA to form 8-hydroxy-2-deoxyguanosine DNA adducts (8-OH-dG). The single strand breaks (SSB) that can result from failed base excision repair of these adducts were considered as an effect downstream from 8-OH-dG. We previously demonstrated that, in the presence of effective base excision repair, 8-OH-dG can exhibit threshold-like dose-response dependence, while the downstream SSB can still exhibit a linear dose-response. Here we demonstrate that this result holds for a variety of conditions, including low levels of GSH, the presence of additional SSB repair mechanisms, or a scavenger. It has been shown that melatonin, a terminal scavenger, inhibits<mml:math xmlns:mml=\"http:\/\/www.w3.org\/1998\/Math\/MathML\" id=\"M2\"><mml:mrow><mml:msub><mml:mrow><mml:mtext>KBrO<\/mml:mtext><\/mml:mrow><mml:mrow><mml:mtext>3<\/mml:mtext><\/mml:mrow><\/mml:msub><\/mml:mrow><\/mml:math>-caused oxidative damage. Our modeling revealed that sustained exposure to<mml:math xmlns:mml=\"http:\/\/www.w3.org\/1998\/Math\/MathML\" id=\"M3\"><mml:mrow><mml:msub><mml:mrow><mml:mtext>KBrO<\/mml:mtext><\/mml:mrow><mml:mrow><mml:mtext>3<\/mml:mtext><\/mml:mrow><\/mml:msub><\/mml:mrow><\/mml:math>can lead to fast scavenger exhaustion, in which case the dose-response shapes for both endpoints are not substantially affected. The results are important to consider when forming conclusions on a chemical\u2019s toxicity dose dependence based on the dose-response of early genotoxic events.<\/jats:p>","DOI":"10.1155\/2015\/764375","type":"journal-article","created":{"date-parts":[[2015,9,11]],"date-time":"2015-09-11T00:19:41Z","timestamp":1441930781000},"page":"1-12","source":"Crossref","is-referenced-by-count":10,"title":["Kinetic Modeling Reveals the Roles of Reactive Oxygen Species Scavenging and DNA Repair Processes in Shaping the Dose-Response Curve of KBrO<sub>3<\/sub>-Induced DNA Damage"],"prefix":"10.1155","volume":"2015","author":[{"given":"Maria A.","family":"Spassova","sequence":"first","affiliation":[{"name":"National Center for Environmental Assessment, Office of Research and Development, U.S. Environmental Protection Agency, Washington, DC 20460, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David J.","family":"Miller","sequence":"additional","affiliation":[{"name":"Division 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