Different sensitivities to ultraviolet light-induced cytotoxicity and sister chromatid exchanges in xeroderma pigmentosum and Bloom's syndrome fibroblasts.

Abstract

The relationship between ultraviolet (UV) light-induced sister chromatid exchanges (SCE) and UV cytotoxicity was compared among fibroblast strains from 18 patients with xeroderma pigmentosum (XP) (6 group A, 1 group C, 3 group D, 5 group E, 3 variant), 2 patients with Bloom's syndrome (BS) and 3 normal subjects. Spontaneous SCE frequencies in all of the XP strains were indistinguishable from those in normal cells, while BS cells exhibited about 10 times more spontaneous SCE than did normal cells. SCE were induced dose-dependently by UV at doses of 0-4.0 J/m2 in all the strains. The mean frequencies of UV-induced SCE were much higher in XP-A and -C cells than in normal cells. XP-D and -E cells were slightly more sensitive to UV-induced SCE formation than normal cells. XP-variant cells were almost as sensitive as normal cells. The induced SCE frequencies plotted as a function of surviving fraction were relatively lower in XP-A and -D cells than those in normal cells, though in XP-C, -E, and -variant cells they were almost the same as those in normal cells, suggesting that, in XP-A and -D groups, UV damage is more lethal than producing SCE in surviving cells. By contrast, 2 BS strains exhibited significantly higher frequencies of UV-induced SCE than the other strains as a function of not only UV dose but also surviving fraction. These results reflect the essential differences between XP and BS cells in UV induction of SCE.