title: Thymidine triphosphate synthesis in senescent WI38 cells. Relationship to loss of replicative capacity.
abstract: The effect of in vitro age on thymidine triphosphate (TTP) synthesis was assessed in WI38 cultures according to the following measurements: (1) thymidine kinase activity of broken cell preparations; (2) in situ incorporation of [3H]thymidine into acid-soluble material; and (3) total intracellular TTP content as determined by an enzymatic assay. All three parameters were maximal in exponentially proliferating populations and minimal in quiescent monolayers; no significant differences between young and old cultures were observed despite the reduced replicative capacity of the latter. The addition of serum to density-arrested cultures induced both TTP synthesis and DNA replication after a lag of approx. 12 h; although a greater percentage of young cells initiated replication as compared with old, pool sizes expanded to a similar extent in both populations. Pool expansion did not require entry into S phase; the pool sizes of control and cytosyl arabinoside-treated cultures were comparable. These findings suggest that senescent cells retain the ability to synthesize TTP, even though they are incapable of replicating DNA. Because TTP synthesis is a cell cycle-dependent event that normally begins in late G1, senescent cells might be blocked in the latter portion of the prereplicative phase and not in G0 as are quiescent cells.
mesh_terms: D002455:Cell Division; D002460:Cell Line; D002470:Cell Survival; D003260:Contact Inhibition; D004247:DNA / Q000096:biosynthesis; D006801:Humans; D007399:Interphase; D007700:Kinetics; D013936:Thymidine / Q000378:metabolism; D013937:Thymidine Kinase / Q000378:metabolism; D013942:Thymine Nucleotides / Q000096:biosynthesis*
chemical_list: D013942:Thymine Nucleotides; D004247:DNA; D013937:Thymidine Kinase; C024157:thymidine 5'-triphosphate; D013936:Thymidine