Abstract

Experimental data suggest that enzymes and substances, which decrease DNA-damage or improve repair can be used as photoprotective agents. These observations have led to the development of new strategies to facilitate DNA-repair in human cells and thereby improve photoprotection [1–3]. UV-irradiation may have deleterious effects on the DNA of skin cells. Indeed, UV-irradiation is capable of inducing extensive DNA-damage that overactivates PARP causing increased energy demand, which in turn may result in collapse of energy metabolism and in cell death. This suggests that moderation of PARP activity following DNA-damage may protect skin cells from the harmful effects of acute and chronic UV-exposure.The effects of BGP-15M, a topically applied novel PARP-inhibitor on UV-induced acute and chronic photodamage were investigated in a hairless mouse model and in human skin. DNA injury was detected by measuring the formation of single-strand DNA breaks and counting sunburn cells. The ADP-ribosylation of PARP was assessed by Western blot analysis. Immunosuppression was investigated in epidermal cells by detecting TNFá and IL-10 expression. UV-induced photocarcinogenesis was determined by clinical, immunohistochemical, and biochemical methods. It has been observed that BGP-15M protects against the clinical and histopathological signs of long-term (26 week) UVA exposure in 8-methoxipsoralen sensitized skin, and decreases the UVB-induced accumulation of mutations and deletions in tumor suppressor genes. Topical treatment with BGP-15M prevents photocarcinogenesis induced by long-term, 32 week-UVB or 26 week-UVA exposure in hairless mice. The above observations carry the promise of a novel type biological skin protective agent against UV-induced photocarcinogenesis, which can revolutionize sun protection in the coming years. References: 1.Yarosh D et al: Lancet, 2001; 357: 926 2.Farkas B et al: Biochem Pharmacol, 2002; 63: 921 3.Farkas B et al: Pharmacology & Toxicology Series, Boca Raton, London, Washington, CRC Press 2002; pp: 257

Keywords: topical PARP-inhibitor, skin cancer, UVA, UVB, photoprotection