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 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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Environmental Health Sciences (NIEHS)
Type
Intramural Research (Z01)
Project #
1Z01ES021229-04
Application #
6837411
Study Section
(LECM)
Project Start
Project End
Budget Start
Budget End
Support Year
4
Fiscal Year
2003
Total Cost
Indirect Cost
Name
U.S. National Inst of Environ Hlth Scis
Department
Type
DUNS #
City
State
Country
United States
Zip Code
Chun, Kyung-Soo; Langenbach, Robert (2007) A proposed COX-2 and PGE(2) receptor interaction in UV-exposed mouse skin. Mol Carcinog 46:699-704
Akunda, Jacqueline K; Chun, Kyung-Soo; Sessoms, Alisha R et al. (2007) Cyclooxygenase-2 deficiency increases epidermal apoptosis and impairs recovery following acute UVB exposure. Mol Carcinog 46:354-62
Fischer, Susan M; Pavone, Amy; Mikulec, Carol et al. (2007) Cyclooxygenase-2 expression is critical for chronic UV-induced murine skin carcinogenesis. Mol Carcinog 46:363-71
Chun, Kyung-Soo; Akunda, Jacqueline K; Langenbach, Robert (2007) Cyclooxygenase-2 inhibits UVB-induced apoptosis in mouse skin by activating the prostaglandin E2 receptors, EP2 and EP4. Cancer Res 67:2015-21
Rao, Jagadeesh S; Langenbach, Robert; Bosetti, Francesca (2005) Down-regulation of brain nuclear factor-kappa B pathway in the cyclooxygenase-2 knockout mouse. Brain Res Mol Brain Res 139:217-24
Wormser, Uri; Langenbach, Robert; Peddada, Shyamal et al. (2004) Reduced sulfur mustard-induced skin toxicity in cyclooxygenase-2 knockout and celecoxib-treated mice. Toxicol Appl Pharmacol 200:40-7