1. ¹Department of Immunology and the Center for Cancer Immunology Research, The University of Texas Graduate School of Biomedical Sciences at Houston, The University of Texas, MD Anderson Cancer Center, Houston, Texas, USA
2. ²Division of Dermatology, Department of Internal Medicine Related, Graduate School of Medicine, Kobe University, Kobe, Japan
3. ³Department of Lymphoma, The University of Texas, MD Anderson Cancer Center, Houston, Texas, USA

Correspondence: Dr Stephen E. Ullrich, Department of Immunology-902, Center for Cancer Immunology Research, The University of Texas, MD Anderson Cancer Center, 1515 Holcombe Blvd., Houston, Texas 77030, USA. E-mail: sullrich@mdanderson.org

Received 14 July 2009; Revised 31 August 2009; Accepted 9 September 2009; Published online 15 October 2009.

Abstract

UV exposure induces skin cancer, in part, by inducing immune suppression. Repairing DNA damage, neutralizing the activity of cis-urocanic acid, and reversing oxidative stress abrogate UV-induced immune suppression and skin cancer induction, suggesting that DNA, UCA, and lipid photo-oxidation serve as UV photoreceptors. What is not clear is whether signaling through each of these different photoreceptors activates independent pathways to induce biological effects or whether there is a common checkpoint where these pathways converge. Here, we show that agents known to reverse photocarcinogenesis and photoimmune suppression, such as platelet-activating factor (PAF) and serotonin (5-HT) receptor antagonists, regulate DNA repair. Pyrimidine dimer repair was accelerated in UV-irradiated mice injected with PAF and 5-HT receptor antagonists. Nucleotide excision repair (NER), as measured by unscheduled DNA synthesis, was accelerated by PAF and 5-HT receptor antagonists. Injecting PAF and 5-HT receptor antagonists into UV-irradiated Xeroderma pigmentosum complementation group A–deficient mice, which lack the enzymes responsible for NER, did not accelerate photoproduct repair. Similarly, UV-induced formation of 8-oxo-deoxyguanosine was reduced by PAF and 5-HT receptor antagonists. We conclude that PAF and 5-HT receptor antagonists accelerate DNA repair caused by UV radiation, which prevents immune suppression and interferes with photocarcinogenesis.