Oral Presentation 18th International Congress on Photobiology 2024

UV carcinogenesis-update- (#32)

Chikako Nishigori 1
  1. Kobe University, Chuou-ku, Kobe, Japan

Previously UV carcinogenesis has been considered to be cauaed by the accumulation of genetic mutations in cancer-related genes, including oncogenes and tumor suppressor genes such as p53 genes. Researchers have demonstrated that these genetic changes found in skin cancers of sun-exposed body sites are induced by UV, based on the findings that transition type (pyrimidine to pyrimidine or purine to purine) base changes at di-pyrimidine sites are predominated. However, recent finding revealed that UV carcinogenesis includes more complicated process. Especially, an importance of inflammation is emphasized. It became evident that DNA damage causes inflammation. We have shown that in Ogg1 knockout mice, which fail to repair 8-OxoG, manifest much higher frequency of UV-induced skin cancers without the increase in p53 mutations, and gene expression analysis in this system revealed that the presence of 8-oxoG upregulates inflammatory pathway genes. Further, we have shown that the mice model of xeroderma pigmentosum (XP), DNA repair disorder, where patients manifest severe sunburn and high frequency of skin cancers in the sun-exposed body sites, expressed extremely high level of CXCL1, inflammatory chemokine, and to our surprise, inhibiting CXCL1 using neutral antibody markedly decreased the development of UV induced skin cancers, without repairing dipyrimidine photoproduts. In addition, some anti-inflammatory medicine demonstrated the inhibitory effect of developing UV induced skin cancers. Recently the influence of some medicine in clinical use on UV carcinogenesis has been indicated. For example, some epidemiological studies suggested that the use of voriconazole and hydrochlorothiazide at higher dose for longer period might upregulate UV carcinogenesis process. We have experimentally shown the increase in the formation of DNA damage as well as cytokine expression in the presence of hydrochlorothiazide in mice irradiated with UV. In view of UV sources, many newly emerging UV devices are used in our circumstances. For instance, 222 nm-UV drew our attention during the COVID19 pandemic, because of its shallow reach to the surface of the microorganism and failure of penetrating through its cytoplasm into the nucleus. Although information of safety of far-UVC has not been fully accumulated, as far as UV carcinogenesis studies, 222 nm UVC did not produce any skin cancers even in the XP model mice. However, we need to investigate from various view points on the safety of newly emerged UV devices before its use for human.