ULTRAVIOLET-RADIATION-B INDUCES DIFFERENTIATION AND PROTEIN-KINASE-C IN NORMAL HUMAN EPIDERMAL-KERATINOCYTES

Mid-wave ultraviolet radiation (UVB, 280-320 nm) is highly efficient a t inducing erythema, pyrimidine dimers in DNA, oncogene expression and initiation of cutaneous tumors. These UVB-induced responses of epider mal cells have been correlated with the direct effects of UVB on DNA. However, UVB has also been shown to have biologic effects at the cellu lar level that appear to mimic some of the membrane-associated effects produced by phorbol ester tumor promoters such as 12-O-tetradecanoyl phorbol-13-acetate (TPA). For example, we have previously shown that b oth UVB irradiation and TPA treatment are followed by release of arach idonic acid and a rapid, dose-dependent inhibition of epidermal growth factor (EGF) binding. TPA generates cellular responses through activa tion of a phospholipid-dependent, calcium-sensitive protein kinase, pr otein kinase C (PKC). The primary goal of the studies described here w as to compare the cellular effects of TPA with those of UVB with speci al regard to PKC and keratinocyte growth control, using normal human e pidermal keratinocytes. The results obtained showed that both TPA and UVB radiation induced differentiation in normal human keratinocytes. U VB radiation, however, increased both cytosolic and membrane-associate d levels of PKC, in contrast to TPA, which increased PKC primarily in the membrane fraction. PKC is probably not the initial chromophore or target molecule of UVB, but because activation of PKC has been shown t o be essential for keratinocyte differentiation, differentiation induc ed by UVB may be caused by activation of PKC by UVB-induced release of diacylglycerol or arachidonic acid.