Apoptosis and efficient repair of DNA damage protect human keratinocytes against UVB.

UVB irradiation is a mutagen, a tumor promoter and a complete carcinogen. Keratinocytes are the primary target for UVB-induced human cutaneous malignancies. In this study a systematic comparison of UVB response in human primary keratinocytes and fibroblasts was undertaken to reveal whether epidermal cells are provided of specific strategies to maintain genomic integrity. We show that keratinocytes are more resistant to the lethal effects of UVB than fibroblasts and undergo apoptosis at UVB doses which are ineffective in fibroblasts. Following equal UVB doses, keratinocytes present a slightly lower level of DNA photoproducts and repair pyrimidine dimers more efficiently than fibroblasts. In addition, their cell cycle progression is largely unaffected after UVB doses that cause an abrupt G1/S arrest in fibroblasts. These peculiar features are associated with a rapid but very transitory p53 response to UVB. Our results are consistent with a model in which apoptosis coupled with an efficient DNA repair prevent the replication of aberrant keratinocytes reducing the frequency of mutated cells and consequently the risk of skin cancer development.