High rate of sister chromatid exchanges of Bloom's syndrome chromosomes is corrected in rodent human somatic cell hybrids.

Abstract

The high rate of sister chromatid exchange (SCE) characteristic of cultured somatic cells from patients with Bloom's syndrome (BS) was found to be fully corrected in BS chromosomes retained by somatic cell hybrids between Chinese hamster cells (CHO-YH 21) and BS fibroblasts (GM 1492), independent of the type and the number of human chromosomes retained. On the contrary, the average rate of SCE per Chinese hamster chromosome remained unaffected by hybridization with both BS and normal human cells. A partial suppression of SCE of about 30% was observed in the BS cells themselves when these were co-cultivated with Chinese hamster/Bloom's syndrome hybrid cells. In these hybrids, the rate of SCE per chromosome (Chinese hamster or human) was unaffected by co-cultivation. The data reported indicate that the high rate of SCE in BS cells must be considered to be the consequence of a lost normal function, rather than the acquisition of a new abnormal one, and that several independent genetic systems may be involved in the control of SCE during the replication of mammalian cells. Accordingly, the high rate of SCE in a cultured cell line or an individual should be looked upon as the common phenotype resulting from mutation(s) at any one of these systems. The occurrence of genetic complementation for SCE across the species barrier suggests that at least some of these genetic systems are homologous in different mammalian species and emphasizes the potential(s) of somatic cell hybridization for studying the biology of SCE, in general, and the genetics of Bloom's syndrome, in particular.