Phenotypical characteristics of cultured primary keratinocytes and HaCaT cells exposed to UVA radiation. Ultraviolet A (UVA, 315-400 nm) radiation penetrates the epidermis of the skin in substantial amounts and is recognized as a major factor in the development of skin cancer. The molecular events underlying UVA induced skin carcinogenesis are well documented, but little is known about the phenotypic and functional properties of primary keratinocytes and the widely used HaCaT keratinocyte cell line after UVA radiation. We studied cell cycle, expression of involucrin, filaggrin and loricrin and apoptosis of HaCaT and primary keratinocytes. We demonstrate that UVA radiation results in a significant retardation in the growth and proliferation of keratinocytes, in a parallel decrease of cells expressing filaggrin and an upregulation of involucrin and loricrin. Exposure to UVA radiation induces a concentration dependent upregulation of involucrin in HaCaT and primary keratinocytes, but not loricrin. UVA irradiation of HaCaT and primary keratinocytes results in significant apoptosis. These findings strongly suggest that the UVA radiation-induced impairment in keratinocyte growth may be related to the inability of keratinocytes to maintain normal physiological levels of involucrin. Moreover, exposure of HaCaT and primary keratinocytes to UVA radiation induces proapoptotic signals which may contribute to the loss of keratinocytes and, ultimately, to the development of skin cancer.