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We tested this concept in human melanoma cells cultured in either Ham's F10 medium to maintain amelanotic phenotype or DMEM to induce\/stimulate melanin production, respectively; <jats:italic>N<\/jats:italic>\u2010phenylthiourea (PTU) and <jats:sc>D<\/jats:sc>\u2010penicillamine were used as an inhibitor of melanogenesis. Melanogenic activity was evaluated by visual inspection (color of cell pellets) or by measurement of tyrosinase (dopa oxidase) activity assay. Amelanotic cells or cells with various melanin content were exposed to gamma radiation and tested for viability and colony forming capability. Gamma radiation at doses of 2\u201315 Gy inhibited cell viability and colony forming efficiency in dose\u2010 and time\u2010dependent manner, but pigmented melanoma cells were significantly more resistant to gamma radiation than nonpigmented cells (<jats:italic>p<\/jats:italic> &lt; 0.05\u20130.001). Both PTU and <jats:sc>D<\/jats:sc>\u2010penicillamine inhibited strongly tyrosinase activity and melanin production in melanoma cells (<jats:italic>p<\/jats:italic> &lt; 0.05\u20130.001). Furthermore, inhibition of melanogenesis by PTU or <jats:sc>D<\/jats:sc>\u2010penicillamine resulted in enhancement of melanoma cells sensitivity to killing by gamma rays. In conclusion, the results of these cell culture experiments give support to a clinical trial of pharmacologically induced decrease in melanin synthesis to enhance the efficacy of radiotherapy in advanced melanomas. \u00a9 2008 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/ijc.23664","type":"journal-article","created":{"date-parts":[[2008,6,19]],"date-time":"2008-06-19T18:43:29Z","timestamp":1213901009000},"page":"1448-1456","source":"Crossref","is-referenced-by-count":130,"title":["Inhibition of melanogenesis as a radiation sensitizer for melanoma therapy"],"prefix":"10.1002","volume":"123","author":[{"given":"Anna A.","family":"Bro\u017cyna","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lester","family":"VanMiddlesworth","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrzej 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