The effect of phorbol esters on the proliferation of C3H-10T1/2 mouse fibroblasts: Consideration of both stimulatory and inhibitory effects

✍ Scribed by L. David Tomei; John C. Cheney; Charles E. Wenner

• Publisher: John Wiley and Sons
• Year: 1981
• Tongue: English
• Weight: 372 KB
• Volume: 107
• Category: Article
• ISSN: 0021-9541
• DOI: 10.1002/jcp.1041070310

✦ Synopsis

Abstract

TPA stimulates cell cycle activation in both serum‐deprived and density‐inhibited cultures. The cells reestablish cycle arrest after no more than one generation, and addition of fresh drug produces no further response. However, cells freshly trypsinized can respond with a series of repetitive generations resulting in 3.5–4.0 population doublings over 72 hrs. In kinetic pulse experiments TPA enhanced ^3^H‐thymidine incorporation in densityinhibited cells stimulated by fresh serum but only after markedly suppressing incorporation 8–13 hrs after serum stimulation. When cells arrested by serum deprivation were pretreated with TPA, fresh serum stimulation led to initiation of ^3^H‐TdR incorporation 5 hrs earlier than untreated controls. However, TPA addition at the time of serum stimulation did not lead to a suppression at 8–13 hrs, whereas enhancement was observed during peak incorporation times regardless of whether the cells were pretreated with TPA during serum deprivation. The results support the concept that there can exist within G~1~ multiple states of responsiveness to phorbol esters. These pharmacologically induced states may be correlated with corresponding physiological states of the G~1~ phase of cell cycle.