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The Overexpression of Bcl-2 Inhibits UVA-mediated Immediate Apoptosis in Rat 6 Fibroblasts: Evidence for the Involvement of Bcl-2 as an Antioxidant¹

School of Pharmacy and Pharmacology, University of Bath, Bath BA2 7AY, United Kingdom [C. P., R. M. T.]; Swiss Institute for Experimental Cancer Research, CH-1066 Epalinges, Switzerland [G. R., O. R.]; and Biochemistry Institute, University of Fribourg, CH-1700 Fribourg, Switzerland [C. B.]

We examined the effect of broad spectrum UVA (320–380 nm) and UVB (290–320 nm) radiation on the induction of apoptosis in the rat 6 fibroblast cell line (R6). UVA, but not UVB, induces apoptosis in this cell line. The morphological changes and DNA ladders associated with apoptosis occurred within the first 4 h after UVA irradiation, a phenomenon referred to as "immediate" apoptosis. From previous studies, it is known that Bcl-2 inhibits most types of apoptotic cell death. Overexpression of mouse Bcl-2 in the R6 fibroblasts inhibited the UVA-induced immediate apoptosis. The induction of the heme oxygenase 1 (HO-1) gene by UVA is a general response to oxidative stress. As a marker of oxidative stress, we monitored the effect of Bcl-2 overexpression on the level of HO-1 mRNA accumulation after UVA irradiation. The results showed that the overexpression of Bcl-2 in the R6 fibroblasts strongly reduces the level of HO-1 induction from 12.5- to 4.9-fold. We propose that Bcl-2 expression inhibits UVA-induced immediate apoptosis via an antioxidant pathway, suppressing either the generation or effects of specific UVa-mediated reactive oxygen species.

¹ This work was supported by a core grant from the Association for International Cancer Research (United Kingdom), as well as grants from the League Against Cancer of Central Switzerland, the Neuchateloise League Against Cancer, and the Swiss National Science Foundation.

² To whom requests for reprints should be addressed, at School of Pharmacy and Pharmacology, University of Bath, Bath BA2 7AY, United Kingdom.

Received 10/14/96. Accepted 2/17/97.

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