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The purpose of this study was to determine the relationship between loss of <jats:italic>INK4a\/Arf<\/jats:italic> activity and inflammation in the development of ultraviolet (UV) radiation\u2010induced skin tumors. Panels of <jats:italic>INK4a\/Arf<\/jats:italic><jats:sup><jats:italic>\u2010\/\u2212<\/jats:italic><\/jats:sup> mice and wild\u2010type (WT) mice were treated with a single dose of UVB (200\u00a0mJ\/cm<jats:sup>2<\/jats:sup>). For long\u2010term studies, these mice were irradiated with UVB (200\u00a0mJ\/cm<jats:sup>2<\/jats:sup>) three times weekly for 30\u00a0weeks. At the end of the experiment, tissues were harvested from mice and assayed for inflammatory biomarkers and cytokines. A single dose of UVB resulted in a significant increase in reactive oxygen species (ROS) and 8\u2010dihydroxyguanosine (8\u2010oxo\u2010dG) lesions in <jats:italic>INK4a\/Arf<\/jats:italic><jats:sup><jats:italic>\u2212\/\u2212<\/jats:italic><\/jats:sup> mice compared to WT mice. When subjected to chronic UVB, we found that 100% of <jats:italic>INK4a\/Arf<\/jats:italic><jats:sup><jats:italic>\u2212\/\u2010<\/jats:italic><\/jats:sup> mice had tumors, whereas there were no tumors in WT controls after 24\u00a0weeks of UVB exposure. The increase in tumor development correlated with a significant increase in nuclear factor (NF)\u2010\u03baB, cyclooxygenase\u20102 (COX\u20102), prostaglandin E<jats:sub>2<\/jats:sub> (PGE<jats:sub>2<\/jats:sub>) and its receptors both in UVB\u2010exposed skin and in the tumors. A significant increase was seen in inflammatory cytokines in skin samples of <jats:italic>INK4a\/Arf<\/jats:italic><jats:sup><jats:italic>\u2010\/\u2010<\/jats:italic><\/jats:sup> mice following treatment with chronic UVB radiation. Furthermore, significantly more CD11b<jats:sup>+<\/jats:sup>Gr1<jats:sup>+<\/jats:sup> myeloid cells were present in UVB\u2010exposed <jats:italic>INK4a\/Arf<\/jats:italic><jats:sup><jats:italic>\u2010\/\u2010<\/jats:italic><\/jats:sup> mice compared to WT mice. Our data indicate that by targeting UVB\u2010induced inflammation, it may be possible to prevent UVB\u2010induced skin tumors in individuals that carry <jats:italic>CDKN2A<\/jats:italic> mutation.<\/jats:p>","DOI":"10.1111\/exd.13356","type":"journal-article","created":{"date-parts":[[2017,4,18]],"date-time":"2017-04-18T13:55:18Z","timestamp":1492523718000},"page":"1018-1025","source":"Crossref","is-referenced-by-count":6,"title":["Loss of <i>INK4a\/Arf<\/i> gene enhances ultraviolet radiation\u2010induced cutaneous tumor development"],"prefix":"10.1111","volume":"26","author":[{"given":"Israr","family":"Ahmad","sequence":"first","affiliation":[{"name":"Department of Dermatology University of Alabama at Birmingham  Birmingham AL USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Purushotham","family":"Guroji","sequence":"additional","affiliation":[{"name":"Department of Dermatology University of Alabama at Birmingham  Birmingham AL 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