Irradiation with ultraviolet-A (UVA) ray at doses of 20-100 J/cm(2) diminished the cell viability of human keratinocytes HaCaT and human melanoma cells HMV-II, both of which were protected by pre-irradiational administration with the ascorbic acid (Asc) derivative, VC-IP (2,3,5,6-O-tetra-2'-hexyldecanoyl-L-ascorbic acid; vitamin C-isopalmityl tetraester), which is the first lipoidic-liquiform pro-vitamin C by itself that is materialized by esterization of all four intramolecular hydroxyl groups of an Asc molecule with branched chain fatty groups, resulting in molecular fluidity higher than that of the corresponding straight chains. Irradiation with UVA to HaCaT keratinocytes was shown to cause the formation of 8-hydroxydeoxyguanosine (8-OHdG), translocation of phosphatidylserine in the inner layer into the outer layer of cell membrane, and lowering of a mitochondrial membrane potential, all of which were repressed by pre-irradiational administration with VC-IP. Expression of p53 gene, another hallmark of UV-induced DNA damages, was promoted by UVA irradiation to the keratinocytes but also repressed by VC-IP. Administration with VC-IP of 10-50 microM to human fibroblasts NHDF achieved the enhancement of collagen synthesis, repression of matrix metalloprotease-2/9 activity, and increasing of intracellular Asc contents more markedly than that with Asc itself of the same concentrations. Thus UVA-induced diverse harmful effects could be prevented by VC-IP, which was suggested to ensue intrinsically from the persistent enrichment of intracellular Asc, through esterolytic conversion of VC-IP to a free-form Asc molecule, resulting in relief to UVA-caused oxidative stress.