摘要
Background: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. Objectives:To examine the effect of UVA1 on the activation of p53 by phosphorylation, which has not yet been studied. Methods: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 12 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. Results 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). Conclusions: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.
Background: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. Objectives:To examine the effect of UVA1 on the activation of p53 by phosphorylation, which has not yet been studied. Methods: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 12 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. Results 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). Conclusions: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.
