De novo synthesis of glutathione is required for both entry into and progression through the cell cycle
✍ Scribed by Martin Poot; Heidi Teubert; Peter S. Rabinovitch; Terrance J. Kavanagh
- Publisher
- John Wiley and Sons
- Year
- 1995
- Tongue
- English
- Weight
- 540 KB
- Volume
- 163
- Category
- Article
- ISSN
- 0021-9541
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✦ Synopsis
Abstract
To study the putative role of de novo synthesis of glutathione (GSH) in the regulation of the cell cycle, we exposed NIH‐3T3 cells to buthionine sulfoximine (BSO) and analysed cell cycle kinetics with continuous bromodeoxyuridine (BrdU) labeling and bivariate Hoechst 33258/ethidium bromide flow cytometry. Treating quiescent cells, which themselves had a low GSH content, with BSO did not affect subsequent entry into and progression through the cell cycle. Adding BSO during serum stimulation, however, provoked a dose‐dependent inhibition of cell growth and a delayed increase in GSH level. The cell kinetic mechanism underlying BSO‐induced growth inhibition is a diminished entry into the cell cycle and a permanent arrest in the S and G2 phase of the cell cycle. Our results are consistent with the hypothesis that GSH de novo synthesis is required for cell activation and proper S and G2 phase transit. © 1995 Wiley‐Liss, Inc.