Inhibition of ornithine decarboxylase activity and cell proliferation by ultraviolet B radiation in EGF-stimulated cultured human epidermal keratinocytes

J Invest Dermatol. 1993 Jul;101(1):54-8. doi: 10.1111/1523-1747.ep12359508.


Irradiation of EGF-stimulated human keratinocytes in vitro with ultraviolet B (UVB) radiation inhibited both ornithine decarboxylase (ODC) activity and cellular proliferation. A dose-dependent reduction in ODC activity occurred in primary cultures of adult facial keratinocytes and neonatal foreskin keratinocytes, and in an SV40-transformed keratinocyte cell line derived from neonatal foreskin. When SV40-transformed keratinocytes were treated with epidermal growth factor (EGF), ODC activity was induced up to 21 times in the absence of ultraviolet radiation. However, pre-treatment with UVB significantly reduced the EGF induction of ODC. For example, 85% less ODC activity was observed in cultures treated with EGF (10 ng/ml) plus 2.5 mJ/cm2 of UVB than cultures treated with EGF alone. To assess the effect of UVB on cell proliferation, normal human epidermal keratinocytes grown in medium containing EGF were irradiated with 5 and 10 mJ/cm2 UVB. At days 3 and 5 post-irradiation a significant (up to 78%) decrease in proliferation was observed. Nevertheless, the mean proportion of viable to dead cells remained similar in both UVB-treated and non-irradiated cell cultures. Northern blot analysis of total RNA isolated from irradiated and sham-irradiated cultures showed that UVB caused approximately a one third reduction in steady-state ODC mRNA levels in EGF-stimulated keratinocyte cultures. Because ODC is an enzyme required for cell proliferation, we propose that the UVB-induced decrease in cell proliferation may result at least in part from UVB inhibition of ODC mRNA accumulation and reduced enzyme activity.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Cell Division / drug effects
  • Cell Division / radiation effects
  • Cells, Cultured
  • Epidermal Cells
  • Epidermal Growth Factor / pharmacology*
  • Epidermis / metabolism*
  • Epidermis / radiation effects*
  • Humans
  • Keratinocytes / drug effects
  • Keratinocytes / metabolism*
  • Keratinocytes / radiation effects*
  • Ornithine Decarboxylase / genetics
  • Ornithine Decarboxylase Inhibitors*
  • RNA, Messenger / metabolism
  • Ultraviolet Rays*


  • Ornithine Decarboxylase Inhibitors
  • RNA, Messenger
  • Epidermal Growth Factor
  • Ornithine Decarboxylase