The replicative life spans of euploid hybrids derived from short-lived and long-lived human skin fibroblast cultures.

Two recent technical advances facilitate the derivation of proliferating hybrids from human diploid fibroblast strains without recourse to biochemical selection: (1) a new chemically-mediated method of somatic cell fusion (PEG-DMSO) yields hybrids at rates as high as 1 in 160 colonies after dilute plating of treated cell mixtures, and (2) a simple technology for assessment of DNA content (flow microfluorometry) permits rapid and highly sensitive monitoring of ploidy. Employing these techniques, we isolated 43 chromosomally stable hybrid clones from 12 crosses between seven different strains representing a wide range of longevities. Crosses between short-lived strains resulted in short-lived hybrid offspring, whereas hybrids derived from long-lived parents tended to be long-lived. Crosses between strains of contrasting longevities gave clones with intermediate growth potentials relative to the other types of hybrids. The failure to observe complementation (enhanced longevity) of hybrids argues against random recessive single-copy gene mutations as important determinants of clonal senescence.