619 CP31398, which reverses UV-induced p53 mutations, does not undo ultraviolet radiation-induced immune suppression

Abstract

Chronic, excessive exposure to solar ultraviolet radiation is the major causative agent for cutaneous squamous cell carcinomas. Mutations in p53 are essential for these cancers to develop. UV radiation is also immunosuppressive and is an additional requirement for UV-induced SCCs to develop. Mutations in p53 can be reversed with the compound CP31398, which results in fewer SCCs in mice exposed to a UV radiation skin carcinogenesis protocol. It is unknown whether p53 mutations contribute to photoimmunosuppression. The purpose of this study was to determine if the UV immunosuppressive effects could be reversed by pretreatment with CP31398. A local UVB regimen consisting of UVB radiation (200 mJ/cm2) for 4 days followed by sensitization with the hapten 2, 4, dinitrofluorobenzene (DNFB) was employed for photoimmunosuppression. To determine the role of CP-31398, we treated the shaved dorsal skin of C57BL/6 mice with CP-31398 (1.25 mg/mouse) or vehicle cream, 30 min before each UVB treatment. Treatment with CP-31398 did not abrogate the immunosuppressive effect of UV. These findings suggest that although p53 mutations are responsible for UV-induced SCCs, they are not necessary for UV-induced immunosuppression.