Failure of infinite life span human cells from different immortality complementation groups to yield finite life span...

The observation that fusion of infinite life span cells with finite life span cells produces hybrid cells with finite life spans led to the conclusion that an infinite life span in culture is a recessive trait resulting from loss of the function of a gene or genes that contribute to an active program for cellular senescence. Furthermore, finding that certain pairs of infinite life span cells, when fused to one another, can complement each other to yield finite life span hybrids allowed 30 infinite life span cell lines to be assigned to four immortality complementation groups (Pereira-Smith and Smith, 1988, Proc. Natl. Acad. Sci. U.S.A., 85:6042). In the present study, we fused a chromosomally stable, near diploid, morphologically normal, infinite life span cell strain, designated MSU-1.1, with its normal, finite life span, precursor cell strain and obtained finite life span hybrids, as expected if infinite life span in culture is a recessive trait. However, 14 of the 14 hybrids from our fusions of MSU-1.1 cells with representative cell lines from each of the four immortality complementation groups, and 38 of the 39 hybrids from our fusions of infinite life span cells that have been reported to complement each other, failed to exhibit finite life spans. This result suggests that infinite life span cells cannot complement each other to yield finite life span hybrids. In examining this unexpected result, we obtained evidence that long-term dual drug selection can be deleterious to hybrid cells even though they carry resistance markers for both drugs, indicating that the cell death of such hybrids observed in other studies may have resulted from the cytotoxic effect of long-term drug selection, rather than from senescence.