{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T00:46:46Z","timestamp":1788914806663,"version":"build-2803163510"},"reference-count":57,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2001,6,29]],"date-time":"2001-06-29T00:00:00Z","timestamp":993772800000},"content-version":"vor","delay-in-days":179,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Environ and Mol Mutagen"],"published-print":{"date-parts":[[2001,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The DNA damage induced by <jats:italic>N<\/jats:italic>\u2010hydroxy\u20104\u2010acetylaminobiphenyl (N\u2010OH\u2010AABP), the proximate carcinogenic metabolite of the human bladder carcinogen 4\u2010aminobiphenyl (ABP), was examined in human transitional cell carcinoma (TCC) cells after exposure to the chemical in vitro. <jats:sup>32<\/jats:sup>P\u2010postlabeling analysis of TCC cultures exposed to N\u2010OH\u2010AABP revealed a minor adduct identified as 3\u2010(deoxyguanosin\u2010<jats:italic>N<\/jats:italic><jats:sup>2<\/jats:sup>\u2010yl)\u20104\u2010acetylaminobiphenyl (dG\u2010N2\u2010AABP) based on comparison of the HPLC and TLC mobility of the product with the synthetic standard. An adduct with the same chromatographic properties was also detected on postlabeling analyses of calf thymus DNA bound to N\u2010OH\u2010AABP by incubation with horseradish peroxidase and hydrogen peroxide. Detection of dG\u2010N2\u2010AABP, which contains the acetyl moiety, suggests that <jats:italic>N<\/jats:italic>\u2010acetoxy\u20104\u2010acetylamino\u2010biphenyl might be formed as a reactive intermediate and could conceivably arise by a free\u2010radical\u2013mediated reaction of N\u2010OH\u2010AABP with endogenous peroxidases. The radical intermediates could also form reactive oxygen species (ROS). To test this possibility, TCC cultures were exposed to N\u2010OH\u2010AABP and the formation of ROS was measured using 2,7\u2010dichlorofluorescein (DCF) fluorescence assay. TCC cultures exposed to N\u2010OH\u2010AABP showed a dose\u2010dependent increase in the ratio of DCF\/DNA fluorescence compared to the untreated controls. Formation of ROS was inhibited by butylated hydroxyanisole (BHA). Furthermore, oxidative DNA damage resulting from ROS was monitored by measurement of 8\u2010oxoguanine products by immunochemical staining and the TCC cells treated with N\u2010OH\u2010AABP revealed a characteristic staining. These results suggest that N\u2010OH\u2010AABP caused oxidative DNA damage as well as bulky covalent adducts in urothelial DNA, possibly involving endogenous peroxidases. These findings show that human uroepithelial cells, which are the target cell types in vivo for arylamine\u2010induced cancers, are metabolically capable of activating these proximate carcinogenic metabolites of arylamines, and these reactions might play a determinate role in the genotoxicity of these environmental carcinogens. Environ. Mol. Mutagen. 38:1\u201311, 2001 \u00a9 2001 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/em.1044","type":"journal-article","created":{"date-parts":[[2002,8,25]],"date-time":"2002-08-25T21:50:36Z","timestamp":1030312236000},"page":"1-11","source":"Crossref","is-referenced-by-count":20,"title":["DNA damage in human transitional cell carcinoma cells after exposure to the proximate metabolite of the bladder carcinogen 4\u2010aminobiphenyl"],"prefix":"10.1002","volume":"38","author":[{"given":"Melissa S.","family":"Burger","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer 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