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Human neoplastic transformation due to DNA damage poses an increasing global healthcare concern. Maintaining genomic integrity is crucial for avoiding tumor initiation and progression. The present study aimed to investigate the efficacy of an apple flavonoid fraction (AF4) against various carcinogen\u2010induced toxicity in normal human bronchial epithelial cells and its mechanism of DNA damage response and repair processes. <jats:italic>Methods and Results<\/jats:italic>. AF4\u2010pretreated cells were exposed to nicotine\u2010derived nitrosamine ketones (NNK), NNK acetate (NNK\u2010Ae), methotrexate (MTX), and cisplatin to validate cytotoxicity, total reactive oxygen species, intracellular antioxidants, DNA fragmentation, and DNA tail damage. Furthermore, phosphorylated histone (<jats:italic>\u03b3<\/jats:italic>\u2010H2AX) and proteins involved in DNA damage (ATM\/ATR, Chk1, Chk2, and p53) and repair (DNA\u2010PKcs and Ku80) mechanisms were evaluated by immunofluorescence and western blotting, respectively. The results revealed that AF4\u2010pretreated cells showed lower cytotoxicity, total ROS generation, and DNA fragmentation along with consequent inhibition of DNA tail moment. An increased level of <jats:italic>\u03b3<\/jats:italic>\u2010H2AX and DNA damage proteins was observed in carcinogen\u2010treated cells and that was significantly (<jats:italic>p<\/jats:italic> \u2264 0.05) inhibited in AF4\u2010pretreated cells, in an ATR\u2010dependent manner. AF4 pretreatment also facilitated the phosphorylation of DNA\u2010PKcs and thus initiation of repair mechanisms. <jats:italic>Conclusion<\/jats:italic>. Apple flavonoids can protect in vitro oxidative DNA damage and facilitate repair mechanisms.<\/jats:p>","DOI":"10.1155\/2017\/1767198","type":"journal-article","created":{"date-parts":[[2017,6,18]],"date-time":"2017-06-18T21:02:17Z","timestamp":1497819737000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":35,"title":["Apple Flavonoids Suppress Carcinogen\u2010Induced DNA Damage in Normal Human Bronchial Epithelial Cells"],"prefix":"10.1155","volume":"2017","author":[{"given":"Vazhappilly Cijo","family":"George","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3435-0052","authenticated-orcid":false,"given":"H. P. 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