| First Author | Sreevidya CS | Year | 2010 |
| Journal | J Invest Dermatol | Volume | 130 |
| Issue | 5 | Pages | 1428-37 |
| PubMed ID | 19829299 | Mgi Jnum | J:159966 |
| Mgi Id | MGI:4453114 | Doi | 10.1038/jid.2009.329 |
| Citation | Sreevidya CS, et al. (2010) Agents that reverse UV-Induced immune suppression and photocarcinogenesis affect DNA repair. J Invest Dermatol 130(5):1428-37 |
| abstractText | 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. |
