The effect of ultraviolet (UV) A1, UVB and solar-simulated radiation on p53 activation and p21Waf1/Cip1

High-dose ultraviolet (UV) A1 therapy (doses in the order of 130 J cm(-2)) is effective for atopic dermatitis and scleroderma. UVA1 has been shown to induce a dose-dependent increase in p53 expression in keratinocytes. To examine the effect of UVA1 on the activation of p53 by phosphorylation, which has not yet been studied. Five adult volunteers were exposed to dose series of UVA1 (10-100 J cm(-2)) and, for comparison, narrowband UVB (TL-01) (25-550 mJ cm(-2)) and solar-simulated radiation (SSR) (5.6-30 J cm(-2)) on photoprotected buttock skin and the minimal erythema dose (MED) for each was determined at 24 h. Separate sites on the buttock were subsequently irradiated with a 3-MED dose of UVA1, TL-01 and SSR. At 24 h, punch biopsies (4 mm) were taken from each irradiated site and from an adjacent unirradiated control site, and immunohistochemical staining for p53 (Do-1), activation of p53 (assessed by phosphorylation at serine 15 and serine 392) and p21 was performed. Cell staining was expressed as the mean number of cells stained per three high-power fields (HPFs) and as a percentage of 1000 cells. Sunburn cells (SBCs) were also counted per HPF. UVA1 produced negligible numbers of SBCs, relatively little p53 (Do-1) staining (mean +/- SD cell count per HPF 16 +/- 10), no p53 activation and very little evidence of p21 expression (mean +/- SD cell count per HPF 5.3 +/- 7), in contrast to TL-01 (mean +/- SD cell count per HPF of 11.83 +/- 2.1 SBCs, 146.3 +/- 38 for Do-1, 26.6 +/- 15 for serine 15, 14.9 +/- 12 for serine 392 and 77.9 +/- 30 for p21) or SSR irradiation (mean +/- SD cell count per HPF of 3.5 +/- 1.2 SBCs, 147.5 +/- 62 for Do-1, 54 +/- 50 for serine 15, 38.9 +/- 18 for serine 392 and 56.7 +/- 30 for p21). These data indicate that there are fundamental differences in the effects of UVA1 on p53 and its activation pathways compared with TL-01 and SSR, and may in part explain the differential effects of these phototherapies.