title: De novo synthesis of glutathione is required for both entry into and progression through the cell cycle.
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.
authors.affiliation: Department of Human Genetics, University of Würzburg, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Poot
authors.forename: H
authors.initials: H
authors.lastname: Teubert
authors.forename: P S
authors.initials: PS
authors.lastname: Rabinovitch
authors.forename: T J
authors.initials: TJ
authors.lastname: Kavanagh
mesh_terms: D016475:3T3 Cells; D000818:Animals; D006690:Bisbenzimidazole; D001973:Bromodeoxyuridine; D019328:Buthionine Sulfoximine; D002453:Cell Cycle / Q000187:drug effects / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D004996:Ethidium; D005434:Flow Cytometry; D005978:Glutathione / Q000096:biosynthesis*; D008717:Methionine Sulfoximine / Q000031:analogs & derivatives / Q000494:pharmacology; D051379:Mice
chemical_list: D008717:Methionine Sulfoximine; D019328:Buthionine Sulfoximine; D004996:Ethidium; D001973:Bromodeoxyuridine; D005978:Glutathione; D006690:Bisbenzimidazole