1. ¹Inserm U876, Bordeaux, France
2. ²University Victor Segalen Bordeaux 2, Bordeaux, France
3. ³Centre Hospitalier et Universitaire Bab-el-Oued, Algiers, Algeria
4. ⁴Centre Hospitalier Universitaire de Bordeaux, Department of Dermatology, National Reference Center for Rare Skin Diseases, Hôpital St André, Bordeaux, France

Correspondence: Professor A Taïeb, Inserm U876, University Victor Segalen Bordeaux 2, 146 rue Léo Saignat, Bordeaux cedex 33076, France. E-mail: alain.taieb@chu-bordeaux.fr

Received 21 June 2007; Revised 5 September 2007; Accepted 14 September 2007; Published online 18 January 2008.

Abstract

Xeroderma pigmentosum type C (XPC) is a rare autosomal recessive disorder that occurs due to inactivation of the XPC protein, an important DNA damage recognition protein involved in DNA nucleotide excision repair (NER). This defect, which prevents removal of a wide array of direct and indirect DNA lesions, is associated with a decrease in catalase activity. To test the hypothesis of a novel photoprotective approach, we irradiated epidermis reconstructed with XPC human keratinocytes sustainably overexpressing lentivirus-mediated catalase enzyme. Following UVB irradiation, there was a marked decrease in sunburn cell formation, caspase-3 activation and p53 accumulation in human XPC-reconstructed epidermis overexpressing catalase. Moreover, XPC-reconstructed epidermis was more resistant to UVB-induced apoptosis than normal reconstructed epidermis. While not correcting the gene defect, indirect gene therapy using antioxidant enzymes may be of help in limiting photosensitivity in XPC and probably in other monogenic/polygenic photosensitive disorders characterized by ROS accumulation.