Normalisation of sister chromatid exchange frequencies in Bloom's syndrome by euploid cell hybridisation

Abstract

BLOOM'S syndrome (BS) is a rare autosomal recessive genetic disorder characterised by stunted growth, Sun-sensitive telangiectatic erythema of the face and an abnormally high risk of cancer¹. Cultured lymphocytes and fibroblasts from BS patients have a high frequency of spontaneous structural chromosome aberrations and characteristically high levels of sister chromatid exchanges (SCE)². The primary defect at the molecular level is unknown, but the cytological findings are compatible with a deficiency in a DNA repair function³. The presence of a defect of DNA replication is also suggested by the demonstration that the rate of fork motion during replication in BS is slower than normal⁴. German et al.⁵ have reported the coexistence of cells with both high and normal levels of SCE, suggesting that the defect in BS is regulatory. Tice et al.⁶ concluded from co-cultivation experiments that SCE frequency is mediated by a diffusable agent(s) present in the medium of BS fibroblasts. Other investigators, however have shown suppression of SCE in conditions of co-cultivation^7,8. We have clarified the conflict between these results by examining euploid somatic cell hybrids between BS and normal human fibroblasts.