Agents that reverse UV-Induced immune suppression and photocarcinogenesis affect DNA repair.
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.
Sreevidya
Coimbatore S
CS
Department 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.
Fukunaga
Atsushi
A
Khaskhely
Noor M
NM
Masaki
Taro
T
Ono
Ryusuke
R
Nishigori
Chikako
C
Ullrich
Stephen E
SE
D000080242:8-Hydroxy-2'-Deoxyguanosine; D000818:Animals; D004260:DNA Repair / Q000187:drug effects*; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000378:metabolism; D007108:Immune Tolerance / Q000187:drug effects* / Q000276:immunology / Q000528:radiation effects*; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D018384:Oxidative Stress / Q000187:drug effects / Q000276:immunology; D010879:Piperazines / Q000494:pharmacology; D010972:Platelet Activating Factor / Q000494:pharmacology; D017382:Reactive Oxygen Species / Q000378:metabolism; D012702:Serotonin Antagonists / Q000494:pharmacology; D012878:Skin Neoplasms / Q000235:genetics / Q000276:immunology*; D014466:Ultraviolet Rays; D014560:Urocanic Acid / Q000378:metabolism; D014983:Xeroderma Pigmentosum / Q000235:genetics / Q000276:immunology*; D051760:Xeroderma Pigmentosum Group A Protein / Q000235:genetics
D010879:Piperazines; D010972:Platelet Activating Factor; D017382:Reactive Oxygen Species; D012702:Serotonin Antagonists; D051760:Xeroderma Pigmentosum Group A Protein; C497315:Xpa protein, mouse; C048241:1-(1-naphthyl)piperazine; D000080242:8-Hydroxy-2'-Deoxyguanosine; D014560:Urocanic Acid; D003849:Deoxyguanosine