Epidemiological studies indicate that ultra violet (UV) radiation causes skin damage and is a major environmental agent in non-melanoma skin cancer development. The effects of COX-1 and COX-2 deficiency, as well as COX-1 and COX-2 selective inhibitors, in high dose acute UV induced skin damage have been studied. The results indicate that mice deficient in COX-2, but not COX-1, exhibit dose dependent increases in epidermal skin damage and cell death compared to wild type mice. Levels of apoptosis were increased about 2.5 -fold in COX-2 null mice compared to COX-1 null or wild type mice. The COX-2 null mice also recovered from the acute UV induced epidermal damage about the same as the COX-1 null or wild type mice. However, in an ongoing collaborative study with Dr. S Fischer using the COX genotype transferred into the hairless mouse, it has been observed that COX-2 deficiency causes reduced skin tumor formation in chronic low UV dose exposed mice. This paradox of high dose acute effects versus low dose chronic effects is now being investigated.
