Polyadenylated RNA isolated from senescent human diploid fibroblasts (HDF) inhibited DNA synthesis in proliferation-competent cells after microinjection, whereas polyadenylated RNA from young HDF had no inhibitory effect. Polyadenylated RNA from young cells made quiescent by removal of serum growth factors had a slight inhibitory effect on DNA synthesis. The abundance level of inhibitor messenger RNA (mRNA) from senescent cells was estimated at 0.8 and that of quiescent cells at 0.005 percent. These results demonstrate the existence of one or more antiproliferative mRNA's in nonproliferating normal human cells; these RNA's code for factors that either work antagonistically to initiators of DNA synthesis or regulate the expression of the initiators in some way. The abundance level of the inhibitory mRNA in senescent cells indicates the feasibility of developing a complementary DNA probe that will be useful in studying cell cycle control mechanisms.
Rodent × human hybrids containing single human chromosomes are valuable tools in the study of human genetics. Using a retrovirus carrying the neomycin gene, we generated a neomycin-resistant (neor) pool of human diploid fibroblasts. Following fusion of microcells prepared from this pool to mouse A9 cells, we obtained four neor hybrids containing a single human chromosome 2, 3, 5, or 15.
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