Interferon inhibition of thymidine incorporation into DNA through effects on thymidine transport and uptake

Lawrence Pfeffer, Igor Tamm

Research output: Contribution to journalArticle

34 Citations (Scopus)

Abstract

Replenishment of medium after 72 hr of growth of HeLa‐S3 cells in dense suspension cultures increased [3H]‐thymidine uptake into cells and incorporation into DNA, with the levels reaching a peak ∼ 12 hr following medium change; β interferon inhibits the enhanced uptake of [3H]‐thymidine and labeling of DNA in a dose‐dependent manner. Some reduction in these processes is observed at a concentration as low as 1 u/ml, and ∼ 75% inhibition at 640 u/ml. Kinetic analysis has revealed that the rate of labeling of the acid‐soluble pool with [3H]‐thymidine, measured either at 22°C, or 37°C, is reduced in interferon‐treated (640 u/ml, 24 hr) HeLa‐S3 cells. At 22°C, the initial rate of thymidine transport at a high (500 μM) thymidine concentration, determined within the first 30 sec of [3H]‐thymidine addition was depressed by 44% in interferon‐treated HeLa cells. At 37°C, labeled precursors accumulate in acid‐soluble material for ∼ 8 min after the addition of [3H]‐thymidine, after which an apparent equilibrium level is attained. At this temperature, the rate of thymidine uptake and the apparent equilibrium level attained were depressed by 70% in interferon‐treated HeLa cells. The reduced incorporation of [3H]‐thymidine into DNA in interferon‐treated HeLa‐S3 cells can be largely explained by interferon inhibition of thymidine transport and phosphorylation.

Original languageEnglish (US)
Pages (from-to)431-436
Number of pages6
JournalJournal of Cellular Physiology
Volume121
Issue number2
DOIs
StatePublished - Jan 1 1984
Externally publishedYes

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Thymidine
Interferons
DNA
HeLa Cells
Labeling
Phosphorylation
Suspensions
Kinetics
Temperature
Growth

All Science Journal Classification (ASJC) codes

  • Physiology
  • Medicine(all)
  • Clinical Biochemistry
  • Cell Biology

Cite this

Interferon inhibition of thymidine incorporation into DNA through effects on thymidine transport and uptake. / Pfeffer, Lawrence; Tamm, Igor.

In: Journal of Cellular Physiology, Vol. 121, No. 2, 01.01.1984, p. 431-436.

Research output: Contribution to journalArticle

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abstract = "Replenishment of medium after 72 hr of growth of HeLa‐S3 cells in dense suspension cultures increased [3H]‐thymidine uptake into cells and incorporation into DNA, with the levels reaching a peak ∼ 12 hr following medium change; β interferon inhibits the enhanced uptake of [3H]‐thymidine and labeling of DNA in a dose‐dependent manner. Some reduction in these processes is observed at a concentration as low as 1 u/ml, and ∼ 75{\%} inhibition at 640 u/ml. Kinetic analysis has revealed that the rate of labeling of the acid‐soluble pool with [3H]‐thymidine, measured either at 22°C, or 37°C, is reduced in interferon‐treated (640 u/ml, 24 hr) HeLa‐S3 cells. At 22°C, the initial rate of thymidine transport at a high (500 μM) thymidine concentration, determined within the first 30 sec of [3H]‐thymidine addition was depressed by 44{\%} in interferon‐treated HeLa cells. At 37°C, labeled precursors accumulate in acid‐soluble material for ∼ 8 min after the addition of [3H]‐thymidine, after which an apparent equilibrium level is attained. At this temperature, the rate of thymidine uptake and the apparent equilibrium level attained were depressed by 70{\%} in interferon‐treated HeLa cells. The reduced incorporation of [3H]‐thymidine into DNA in interferon‐treated HeLa‐S3 cells can be largely explained by interferon inhibition of thymidine transport and phosphorylation.",
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