Responses to ultraviolet-B in cell lines from hereditary melanoma kindreds

Ultraviolet-B (UV-B) triggers a cascade of events involving cell cycle cont rol genes leading ultimately to DNA repair or apoptosis. The hypothesis exa mined here is that the genetic abnormality predisposing to melanoma affects the ability of the cell to respond appropriately to UV-B, so favouring mut agenesis. Epstein-Barr virus-transformed lymphoblastoid cell lines from her editary melanoma kindreds were irradiated with UV-B, and changes in p53, p2 1 and Bcl-2 expression and cell cycle phase distribution were analysed. Twe nty-two cell lines were tested: 12 carriers of melanoma susceptibility and 10 non-carriers (unaffected first degree relatives). At 24 h after irradiat ion with 50 J/m(2), 15 of the 22 cell lines showed a rise in G(2)/M. After 400 J/m(2), ail the cell lines showed a reduction or loss of G2/M and 17 of the 22 showed an S phase delay. More carriers than non-carriers of melanom a susceptibility showed significant S phase delay after 50 J/m(2) (seven ou t of 12 carriers versus two out of 10 non-carriers). Six of the 10 pairs (c arrier Versus non-carrier) tested showed discordant cell cycle responses; h owever the nature of the difference was not universal. Bcl-2 reduction was seen 4 h post-irradiation in all the carriers and non-carriers. The p53 and p21 responses, although showing some individual variations, were not relat ed to carrier status. These results show individual Variations in response to UV-B irradiation among cell lines from the members of hereditary melanom a kindreds, but no consistent differences between carriers and non-carriers of melanoma susceptibility. (C) 2001 Lippincott Williams & Wilkins.