{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,15]],"date-time":"2026-07-15T22:19:35Z","timestamp":1784153975240,"version":"3.55.0"},"reference-count":40,"publisher":"Oxford University Press (OUP)","issue":"7","license":[{"start":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T00:00:00Z","timestamp":1782864000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"name":"UNC Superfund Research Program","award":["P42ES031007"],"award-info":[{"award-number":["P42ES031007"]}]},{"DOI":"10.13039\/100023004","name":"UNC Center for Environmental Health and Susceptibility","doi-asserted-by":"publisher","award":["P30-ES779 010126"],"award-info":[{"award-number":["P30-ES779 010126"]}],"id":[{"id":"10.13039\/100023004","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007824","name":"American Chemistry Council","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007824","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,7,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Ethylene oxide (EtO) is a highly reactive industrial chemical and known human carcinogen with a mutagenic mode of action (MOA). Its genotoxicity is primarily mediated through alkylation of DNA, forming the mutagenic adduct O6-(2-hydroxyethyl)-2\u2032-deoxyguanosine (O6-HE-dG), albeit in small quantities, and the more abundant but less- or nonmutagenic N7-(2-hydroxyethyl)guanine (N7-HE-G) adduct. However, dose\u2013response relationships of these DNA adducts, particularly at low inhalation exposure levels (&amp;lt; 3\u2009ppm), remain unknown. These data are necessary to inform the biological plausibility of different statistical dose\u2013response models that have been applied to human or animal data used for cancer risk assessment. In this study, B6C3F1 mice were exposed to EtO (0 to 200\u2009ppm) for 6\u2009h\/d over 28 consecutive days. DNA adducts in lung, liver, bone marrow, and mammary gland were quantified using highly sensitive mass spectrometry platforms. N7-HE-G was detected in all tissues and exposure groups, showing linear dose\u2013response relationships in the low-dose range (\u2264 1\u2009ppm) and increased sharply and exposure-disproportionately in the high-dose range (\u2265 50\u2009ppm). Despite high sensitivity, O6-HE-dG was undetectable in any tissue at exposure &amp;lt; 50\u2009ppm, reflecting adduct levels that are below the current quantifiable limit. At higher exposures (\u2265 50\u2009ppm), O6-HE-dG exhibited a dose\u2013response pattern of N7-HE-G. Notably, the mammary gland, despite being anatomically distant from the site of inhalation, exhibited the second-highest levels of both adducts at higher doses. This study provides the first reliable quantitative dose\u2013response evidence of DNA adducts in tumor target and nontarget (liver) tissues across a wide range of EtO exposures. The two DNA adducts differ markedly in their abundance, repairability and mutagenic potential and together provide a molecular MOA dose\u2013response framework to provide the biological foundation for informing quantitative cancer risk assessment and genotoxic hazard characterization.<\/jats:p>","DOI":"10.1093\/toxsci\/kfag063","type":"journal-article","created":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T11:49:11Z","timestamp":1782992951000},"source":"Crossref","is-referenced-by-count":1,"title":["Molecular dosimetry of DNA adducts in mice exposed to ethylene oxide"],"prefix":"10.1093","volume":"209","author":[{"given":"Chih-Wei","family":"Liu","sequence":"first","affiliation":[{"name":"Department of Environmental Sciences and Engineering, University of North Carolina at Chapel Hill , Chapel Hill, NC,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingya","family":"Peng","sequence":"additional","affiliation":[{"name":"Department of Environmental Sciences and Engineering, University of North Carolina at Chapel Hill , Chapel Hill, NC,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiahao","family":"Feng","sequence":"additional","affiliation":[{"name":"Department of Environmental Sciences and Engineering, University of North Carolina at Chapel Hill , Chapel Hill, NC,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haoduo","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Environmental Sciences and Engineering, University of North Carolina at Chapel Hill , Chapel Hill, NC,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xueying","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Environmental Sciences and Engineering, University of North Carolina at Chapel Hill , Chapel Hill, NC,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B Bhaskar","family":"Gollapudi","sequence":"additional","affiliation":[{"name":"Toxicology Consultant , Midland, MI,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abby A","family":"Li","sequence":"additional","affiliation":[{"name":"Exponent, Inc. 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