Clastogenic activity from Bloom syndrome fibroblast cultures

Media from cultures of fibroblasts of six patients with the autosomal recessive disease Bloom syndrome (BS) and from four normal fibroblast strains were analyzed for clastogenic activity towards phytohemagglutinin-stimulated human blood lymphocytes from healthy donors. Clastogenic activity was detected in concentrated ultrafiltrates of media from all six BS strains but none of the normal fibroblast strains. The frequencies of chromosomal aberrations that were induced depended on the concentration of the ultrafiltrates. Addition of bovine superoxide dismutase to the blood lymphocyte cultures strongly suppressed the clastogenic potency of the ultrafiltrates. Unconcentrated conditioned BS media were inactive. From the pore size of the ultrafilters and Sephadex G-10 chromatography it is concluded that the clastogenic material is in the molecular weight range of 1000 to 10,000. The concentrated ultrafiltrates of BS culture media also possessed the capacity to induce sister chromatid exchanges in normal human blood lymphocytes, but with relatively low efficiency. On the basis of these results and by analogy to certain collagen diseases such as systemic lupus erythematosus, we speculate that BS cells are deficient in the detoxification of active oxygen species.