Roles Of Cyclooxygenase-1 And -2 In UV-Induced Skin Canc

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Ultraviolet light is one of the major environmental factors to which humans are exposed and is known to be a significant cause of human skin cancer. Nonsteroidal anti-inflammatory drugs (NSAIDs) reduce several types of cancers in humans and rodents. NSAIDs are believed to act by inhibiting the cyclooxygenases (COX), and we have observed that both COX-1 and COX-2 deficiencies reduce mouse skin papilloma formation by about 80% in the initiation/ promotion model with the data suggesting that altered keratinocyte differentiation may be responsible. Our studies with UV 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-fold in COX-2 null mice compared to COX-1 null or wild type mice. The COX-2 null mice also recovered from the UV induced epidermal damage more slowly then did wild type mice.