Role of stress responses in human cell survival following exposure to ultraviolet C radiation.
OBJECTIVE
To investigate in human skin and other cells the role of tyrosine kinase and protein kinase-C (PKC) in eliciting cell-signalling responses to UV radiation (UVR) that affect the survival of irradiated cells.


METHODS
The survival of HeLa S3 cells, NCTC 2544 human keratinocytes and A431 human epidermal carcinoma cells was measured following incubation with various tyrosine kinase or PKC inhibitors and exposure to UVC (254nm) radiation. In addition, Western blotting measured PKC isozyme expression in human keratinocytes following UVC exposure.


RESULTS
It was confirmed that inhibition of tyrosine kinase activation reduces the survival of UV-irradiated HeLa S3 cells. However, no effect was seen on the survival of either NCTC 2544 human keratinocytes or A431 human epidermal carcinoma cells. In contrast, specific inhibition of PKC reduced the survival of UV-irradiated keratinocytes but had no effect on HeLa cells. Comparison of the effects of different inhibitors in keratinocytes suggested that this effect was mediated mostly through PKCmu and PKClambda/iota. In addition, keratinocyte exposure to UVC induced large and temporally distinct increases in PKCmu and PKClambda/iota.


CONCLUSIONS
The survival of NCTC 2544 keratinocytes, but not HeLa S3 cells, following UVC exposure is mediated by signalling through PKC, mostly PKCmu and PKClambda/iota. Further study is required to confirm these results in normal human keratinocytes.
National Radiological Protection Board, Chilton, Didcot, UK.
N A
NA
Cridland
M C
MC
Martin
K
K
Stevens
C A
CA
Baller
A J
AJ
Pearson
C M
CM
Driscoll
R D
RD
Saunders
D002294:Carcinoma, Squamous Cell / Q000201:enzymology* / Q000473:pathology; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006367:HeLa Cells / Q000187:drug effects / Q000201:enzymology / Q000473:pathology / Q000528:radiation effects*; D006801:Humans; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000378:metabolism; D015603:Keratinocytes / Q000187:drug effects / Q000201:enzymology / Q000473:pathology / Q000528:radiation effects*; D020935:MAP Kinase Signaling System / Q000187:drug effects / Q000528:radiation effects; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000528:radiation effects; D013312:Stress, Physiological / Q000201:enzymology; D014466:Ultraviolet Rays
D004791:Enzyme Inhibitors; D007527:Isoenzymes; D011505:Protein-Tyrosine Kinases; D011493:Protein Kinase C