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Radiation Protection Dosimetry 91:81-84 (2000)
© 2000 Oxford University Press

The Role of Stress Responses in Determining Cell Fate Following Exposure to Ultraviolet Radiation

N.A. Cridland, M.C. Martin, K. Stevens, C.A. Baller, A.J. Pearson, C.M.H. Driscoll and R.D. Saunders

Cellular stress responses are believed to play an important role in promoting the survival of mammalian cells under adverse conditions, such as exposure to ultraviolet radiation (UVR). Membrane-associated tyrosine kinase activity constitutes an important element of the UV response of HeLa and other non-skin cells. Using a panel of protein kinase inhibitors it was confirmed that tyrosine kinase activation promotes the survival of UV-irradiated HeLa S3 cells, an effect that appeared to be either predominantly or wholly due to an inhibition of epidermal growth factor receptor. In contrast, specific inhibition of protein kinase C (PKC) in ultraviolet-irradiated keratinocytes reduced survival; this treatment had no effect on HeLa cells. Use of a panel of chemical inhibitors exhibiting varying degrees of specificity for different isozymes of PKC suggested that signalling through PKCµ accounts for much of the enhanced survival observed in irradiated keratinocytes, whilst maximal survival appeared to require signalling through another isozyme, probably PKC?/l. Examination of isozyme expression by Western blotting revealed that exposure to UVR induced large but temporally distinct increases in both isozymes.


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