Repeated UVB irradiations do not have the same potential to promote stimulation of melanogenesis in cultured normal human melanocytes

Abstract

The major stimulus for human melanin production is ultraviolet (UV) radiation. Little is known about the mechanisms underlying this response and the eventual enzyme regulation resulting from this activation. We treated normal human melanocytes in culture with daily UVB radiations. Cumulative increases in UVB doses resulted in proportional increases in tyrosinase activity over the first few days whereas an intermittent pattern of tyrosinase activation was observed after the fifth day of irradiation. This intermittent pattern consisted of latency periods where no melanogenic response was elicited despite exposure to UVB. Tyrosinase activity in cellular extracts increased shortly after an effective irradiation, peaked at 3 hours and thereafter decreased to below basal levels. Increased tyrosinase activity was associated with increased amounts of both the newly synthesized and mature forms of the enzyme. Decreased tyrosinase activity following an activation period was correlated with decreases in both the expression of tyrosinase mRNA and the amount of the newly synthesized form of the enzyme present in the melanocytes 24 hours after six irradiations. This particular pattern of stimulation of tyrosinase was not observed in S-91 murine melanoma cells after repeated UVB irradiations. Taken together these results may suggest a photo-protective mechanism developed by irradiated normal human melanocytes.