R. Neades et al., S-PHASE ARREST IN MOUSE KERATINOCYTES EXPOSED TO MULTIPLE DOSES OF ULTRAVIOLET B A RADIATION/, Molecular carcinogenesis (Print), 23(3), 1998, pp. 159-167
Exposure to solar ultraviolet (UV) radiation is believed to cause most
human skin carcinomas. Despite the large body of evidence connecting
UV exposure with skin cancer, the frequency and level of human exposur
e to repetitive doses of UV light will most likely continue for occupa
tional and recreational reasons. By investigating the cellular respons
e of keratinocytes to multiple, physiologically relevant doses of UV,
we hope to better understand the processes involved in UV-induced skin
cancer. In this study, we used a UV exposure model to investigate the
cell-cycle response of keratinocytes exposed to multiple doses of UV-
B/A radiation in which the UV-C component (wavelengths below 290 nm) h
ad been filtered out. Our results indicated that exposure of asynchron
ous mouse keratinocytes to three doses of 200 J/m(2) UV-B/A radiation
at 30 min intervals produced an inhibition of DNA synthesis and S-phas
e arrest between 7 and 25 h after the last irradiation. The S-phase ar
rest was not due to a reduction in the level of cyclin E and A protein
s but was accompanied by inhibition of cyclin-dependent kinase 2 (cdk2
) activity. We observed a similar pattern of cdk2 inhibition induced b
y multiple UV-B/A irradiations in mouse embryo fibroblasts from p21WAF
null mice, indicating that the inhibition of cdk2 was independent of
p21WAF in these cells. (C) 1998 Wiley-Liss, Inc.