Differential Regulation of P53 and Bcl-2 Expression by Ultraviolet A and B

The induction of apoptosis by ultraviolet (UV) radiation and other DNA damaging agents plays a critical role in monitoring the accumulation of genetic damage and the suppression of tumor development. We hypothesize that UVA and UVB induce apoptosis by modulating balances between p53 and/or bcl-2 genes. Using MCF-7 cells that express both wild-type P53 and Bcl-2 proteins, we demonstrated that UVA and UVB induced apoptosis through regulating expression of apoptosis promoting or inhibiting genes. UVA induced immediate apoptosis and downregulated bcl-2 expression. Bcl-2 expression was reduced by ≈40% at 4 h post-150 kJ UVA irradiation per m2 with a maximum downregulation (over 70%) at 24 h. The dose–response studies revealed that significant reduction of bcl-2 expression was observed at UVA doses ranging from 50 to 200 kJ per m2; however, p53 levels were not affected by UVA. In contrast, UVB exhibited a entirely different action than UVA in that UVB substantially induced p53 expression, but had no effect on bcl-2 expression. The induction of P53 by UVB was dose and time dependent with the maximum expression at 24 h post-2 and post-4 kJ UVB irradiation per m2. Downregulation of bcl-2 and fragmentation of DNA induced by UVA occurred earlier (approximately at 4 h) than upregulation of p53 and DNA fragmentation by UVB (12–24 h). These results suggest that UVA and UVB cause cell damage through different mechanisms and that the balances between the expression of p53 and bcl-2 may play an important role in regulating the apoptosis induced by UV irradiation