FAILURE OF INFINITE LIFE-SPAN HUMAN-CELLS FROM DIFFERENT IMMORTALITY COMPLEMENTATION GROUPS TO YIELD FINITE LIFE-SPAN HYBRIDS

The observation that fusion of infinite life span cells with finite li fe 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 th at certain pairs of infinite life span cells, when fused to one anothe r, can complement each other to yield finite life span hybrids allowed 30 infinite life span cell lines to be assigned to four immortality c omplementation groups (Pereira-Smith and Smith, 1988, Proc. Natl. Acad . Sci. U.S.A., 85:6042). In the present study, we fused a chromosomall y stable, near diploid, morphologically normal, infinite life span cel l strain, designated MSU-1.1, with its normal, finite life span, precu rsor cell strain and obtained finite life span hybrids, as expected if infinite life span in culture is a recessive trait. However, 14 of th e 14 hybrids from our fusions of MSU-1.1 cells with representative cel l 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 r esistance markers for both drugs, indicating that the cell death of su ch hybrids observed in other studies may have resulted from the cytoto xic effect of long-term drug selection, rather than from senescence. ( C) 1994 Wiley-Liss, Inc.