Effect of cocultivation on sister chromatid exchange frequencies in Bloom's syndrome and normal fibroblast cells

Abstract

BLOOM'S syndrome (BS) is a rare, autosomal recessive human disorder, characterised by growth retardation, sunlight-induced facial skin eruptions, low immunological competence and a high incidence of cancer^1–4. Lymphocytes, and to a lesser extent, fibroblasts, cultured from affected individuals exhibit unusually high levels of chromosomal aberrations^2,5,6 and sister chromatid exchanges (SCE)^7,8, suggesting that BS cells may be defective in DNA repair and/or synthesis^9–11. However, BS cells are normally competent in excision repair^11–13, postreplication repair¹⁴, single-strand break rejoining¹⁴, and have normal levels of DNA polymerases (α, β, γ)¹⁵. On the other hand, these cytogenetic manifestations of BS could indicate the presence of actual DNA damage, perhaps a consequence of some altered metabolite(s) produced endogenously. To examine this possibility, we assessed the effect of cocultivation of fibroblast cells from a BS individual with those from an unaffected control on SCE frequencies in both cell populations. Results of these studies indicate that BS cells produce an agent(s) capable of causing an increased SCE response in normal cells.