{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T22:39:19Z","timestamp":1792190359969,"version":"4.4.0"},"reference-count":48,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2015,6,24]],"date-time":"2015-06-24T00:00:00Z","timestamp":1435104000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"name":"Basic Science Research Program through the National Research Foundation of Korea (NRF), Ministry of Education","award":["2009-0094027"],"award-info":[{"award-number":["2009-0094027"]}]},{"name":"S & T Support Program for Developing Countries, Ministry of Sciences, ICT, and Future plan","award":["2013K1A3A9A01044071"],"award-info":[{"award-number":["2013K1A3A9A01044071"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Intl Journal of Cancer"],"published-print":{"date-parts":[[2015,12]]},"abstract":"<jats:p>Molecular crosstalk between cancer cells and fibroblasts has been an emerging hot issue in understanding carcinogenesis. As oral submucous fibrosis (OSF) is an inflammatory fibrotic disease that can potentially transform into squamous cell carcinoma, OSF has been considered to be an appropriate model for studying the role of fibroblasts during early stage carcinogenesis. In this sense, this study aims at investigating whether areca nut (AN)\u2010exposed fibroblasts cause DNA damage of epithelial cells. For this study, immortalized hNOF (hTERT\u2010hNOF) was used. We found that the levels of GRO\u2010\u03b1, IL\u20106 and IL\u20108 increased in AN\u2010exposed fibroblasts. Cytokine secretion was reduced by antioxidants in AN\u2010exposed fibroblasts. Increase in DNA double strand breaks (DSB) and 8\u2010oxoG FITC\u2010conjugate was observed in immortalized human oral keratinocytes (IHOK) after the treatment of cytokines or a conditioned medium derived from AN\u2010exposed fibroblasts. Cytokine expression and DNA damage were also detected in OSF tissues. The DNA damage was reduced by neutralizing cytokines or antioxidant treatment. Generation of reactive oxygen species (ROS) and DNA damage response, triggered by cytokines, were abolished when NADPH oxidase (NOX) 1 and 4 were silenced in IHOK, indicating that cytokine\u2010triggered DNA damage was caused by ROS generation through NOX1 and NOX4. Taken together, this study provided strong evidence that blocking ROS generation might be a rewarding approach for cancer prevention and intervention in OSF.<\/jats:p>","DOI":"10.1002\/ijc.29636","type":"journal-article","created":{"date-parts":[[2015,6,16]],"date-time":"2015-06-16T04:03:29Z","timestamp":1434427409000},"page":"2545-2557","source":"Crossref","is-referenced-by-count":43,"title":["Areca nut exposure increases secretion of tumor\u2010promoting cytokines in gingival fibroblasts that trigger\n                    <scp>DNA<\/scp>\n                    damage in oral keratinocytes"],"prefix":"10.1002","volume":"137","author":[{"given":"Rasika P.","family":"Illeperuma","sequence":"first","affiliation":[{"name":"Oral Cancer Research Institute Department of Oral Pathology, Yonsei University College of Dentistry, Seoul  Korea"},{"name":"Faculty of Allied Health Sciences, Department of Medical Laborotary Science University of Peradeniya  Sri 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