DOSE-RATE AND MODE OF EXPOSURE ARE KEY FACTORS IN JNK ACTIVATION BY UV IRRADIATION

Single exposure of cells to UVC (254 nm for 30 s) or to UVB (300 nm fo r 10 min) was shown to activate jun-NH2 kinases which, in turn, phosph orylate their substrates ELK-1, c-jun and ATF-2, While UVC (40-80 J/m( 2)) activates JNK up to 4 h, with maximal induction after 30 min, UVB (150-300 J/m(2)) activates JNK over a prolonged period, up to 24 h, wi th maximal induction after 6 h, UV-mediated activation of src-related tyrosine kinases and MAPK revealed different kinetics, with maximal in duction after 24 h, As recent studies had indicated a role of a UVC co mponent in mediating the ability of UVB to activate JNK, we have exami ned the effect of dose rate as well as of multiplicity of exposures on the activation of these kinases, The UVC portion found in 300 J/m(2) UVB (5%, corresponding to 15 J/m(2), administered within 10 s) did not activate JNK, However, when the same dose was administered at a lower rate (i.e. over 10 min, as needed for UVB irradiation) it was found c apable of activating JNK, MAPK and src kinases, but to a lower degree and with different kinetics than found for UVB, Such differences point to cellular changes which are elicited by UVB, but not UVC, Although a single UVB exposure using a filter that blocks wavelengths below 300 nm prevented activation of JNK, multiple exposures of filtered UVB wa velengths (mimicking chronic exposure) were able to activate JNK, We c onclude that the mode of UVB exposure (dose rate and multiplicity) is a crucial determinant for physiologically relevant activation of JNK.