Cell fusion studies in the Werner syndrome.

The mechanism of retarded DNA synthesis was investigated by the cell fusion method. The [3H] TdR labeling index of young cells from patients with Werner syndrome (WS cells) X young normal human diploid fibroblast cells (NH cells) was considerably lower than that of NH homodikaryons, but was significantly higher than that of WS homodikaryons. The labeling index of old WS X young NH heterodikaryons was as low as that of WS homodikaryons. The labeling index of WS X HeLa heterodikaryons was the same as that of HeLa homodikaryons. These results indicate that WS cells are somewhat similar to senescent NH cells. The labeling indices in both WS karyoplast X NH heterodikaryons and WS cytoplast X NH cybrids were lower than those in normal karyoplast X NH heterodikaryons and normal cytoplast X NH cybrids, respectively. These results indicate that both nuclear and cytoplasmic environments are involved in the retarded DNA synthesis in WS cells. The most plausible interpretation of all our data is that the retarded DNA synthesis in WS cells could be caused by either the 'senescent factor(s)' or the deficiency of gene product(s) that is necessary for DNA synthesis and could be a secondary consequence of the genetic defect.