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1 January 2005 Inverse Relationship Between Increased Apoptosis and Decreased Skin Cancer in UV-irradiated CD1d−/− Mice
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We previously demonstrated that CD1d knockout mice were resistant to ultraviolet (UV)–induced immunosuppression. Because immune suppression is a critical factor in the development of UV-induced skin cancers, we investigated the response of wild type (WT) and CD1d−/− mice to UV carcinogenesis. We found that although 100% of WT mice developed skin tumors after 45 weeks of UV irradiation, only 60% of CD1d−/− mice developed skin tumors. To investigate the mechanisms involved in the resistance of CD1d−/− mice to UV-induced carcinogenesis, we determined the time course and kinetics of keratinocyte cell death after UV irradiation. After acute UV exposure, the terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end-labeling (TUNEL)-positive keratinocytes were eliminated from the skin of WT mice by 72 h post-UV, but they still persisted until 96 h in CD1d−/− mice. The kinetics of p53 protein expression closely followed the kinetics of apoptotic cell death. Chronic UV irradiation resulted in induction of a significantly higher number of apoptotic keratinocytes in CD1d−/− than WT mice. In addition, epidermis and dermis from chronically UV-irradiated CD1d−/− mice harbored significantly fewer p53 mutations than WT mice. These results indicate that the resistance of CD1d−/− mice to UV carcinogenesis may be due to increased cell death and elimination of keratinocytes and fibroblasts containing DNA damage and p53 mutations.

Yasuhiro Matsumura, Angus M. Moodycliffe, Dat X. Nghiem, Stephen E. Ullrich, and Honnavara N. Ananthaswamy "Inverse Relationship Between Increased Apoptosis and Decreased Skin Cancer in UV-irradiated CD1d−/− Mice," Photochemistry and Photobiology 81(1), 46-51, (1 January 2005).
Received: 21 September 2004; Accepted: 1 October 2004; Published: 1 January 2005

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