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 WA and UVB induced apoptosis through regulating expression of apoptosis promoting or inhibiting genes. WA induced immediate apoptosis and downregulated bcl-2 expression. Bcl-2 expression was reduced by approximate to 40% at 4 h post-150 kJ UVA irradiation per m(2) with a maximum downregulation (over 70%) at 24 h. The dose-response studies revealed that significant reduction of bcl-2 expression was observed at WA doses ranging from 50 to 200 kJ per m(2), however, p53 levels were not affected by WA. In contrast, UVB exhibited a entirely different action than WA in that WB 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 WB irradiation per m(2). 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 WA and WB 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.