A potent DNA synthesis inhibitor expressed by the immortal cell line SUSM-1.
We have previously reported the production of DNA synthesis inhibitor proteins by both quiescent and senescent human diploid fibroblasts. Young, proliferating fibroblasts do not produce such inhibitors, but are capable of responding to either the quiescent or senescent cell DNA synthesis inhibitors. Recently, we have analyzed the immortal cell line SUSM-1 (derived from normal liver fibroblasts following exposure to carcinogen) for inhibitory activity. We have found that SUSM-1 cells produce a factor capable of inhibiting DNA synthesis in young fibroblasts. Crude extracts prepared from SUSM-1 cells inhibit DNA synthesis in a dose-dependent manner at concentrations 10-fold lower than those of either senescent or quiescent fibroblast cell extracts. SUSM-1 cells are incapable of responding to the inhibitor they produce, as are three other immortal human cell lines tested. One immortal cell line, HeLa, does respond to the SUSM-1 inhibitor, though to a lesser degree than observed with normal young fibroblasts. One hypothesis is that the DNA synthesis inhibitor protein(s) of senescent cells plays a role in determining the finite in vitro life span of normal cells. The results reported here suggest that SUSM-1 cells may have escaped senescence through loss of a receptor or cofactor for the inhibitor protein(s).
Spiering
A L
AL
Roy M. and Phyllis Gough Huffington Center on Aging, Baylor College of Medicine, Houston, Texas 77030.
Smith
J R
JR
Pereira-Smith
O M
OM
D002457:Cell Extracts / Q000494:pharmacology*; D002460:Cell Line; D002470:Cell Survival; D004261:DNA Replication / Q000187:drug effects*; D005347:Fibroblasts / Q000032:analysis* / Q000166:cytology; D006801:Humans; D013997:Time Factors; D014020:Tissue Extracts / Q000494:pharmacology*
D002457:Cell Extracts; D014020:Tissue Extracts