PMID: 3744936Jul 1, 1986Paper

Effects of glutathione depletion by buthionine sulfoximine on the sensitivity of EMT6/SF cells to chemotherapy agents or X radiation

International Journal of Radiation Oncology, Biology, Physics
D C Shrieve, J W Harris

Abstract

The effects of depletion of cellular glutathione (GSH) on the sensitivity of cultured EMT6/SF cells to chemotherapy agents or x rays under hypoxic and aerated conditions were investigated. Buthionine sulfoximine (BSO), a potent inhibitor of the enzyme gamma-glutamyl-cysteine synthetase, was used to deplete cellular GSH. Addition of BSO (50 microM) to EMT6/SF cultures depleted cellular GSH with a half-time of approximately 2 hr. Cellular GSH reached very low levels within hours of addition of BSO. After removal of BSO, cellular GSH recovered with approximately the same kinetics as was seen for depletion. Incubation of EMT6/SF cells with BSO concentrations of up to 1 mM did not reduce the viability or inhibit growth when exposure was limited to times less than 24 hr. However, for longer exposure times, toxicity and growth inhibition were demonstrated in a dose dependent fashion. EMT6/SF cells were treated with chemotherapy agents under either aerated or extremely hypoxic conditions. Cells were more sensitive to cis-dichlorodiammino Pt(II) (DDP), mitomycin C (MitC), L-phenylalanine mustard (L-PAM), and nitrogen mustard (HN2) when treatment was under hypoxic conditions. The magnitude of this sensitization under hypoxic conditions r...Continue Reading

References

Aug 1, 1979·International Journal of Radiation Oncology, Biology, Physics·J W Harris, D C Shrieve

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Citations

Oct 1, 1991·Journal of Neuro-oncology·M J Allalunis-TurnerR C Urtasun
Sep 1, 1986·International Journal of Radiation Oncology, Biology, Physics·K OnoM Abe
Mar 1, 1989·Cancer Treatment Reviews·D J Stewart, W K Evans
Jul 2, 2005·International Journal of Radiation Oncology, Biology, Physics·Erling T DonnellySara Rockwell
Jan 1, 1990·Critical Reviews in Oncology/hematology·C N Coleman, A T Turrisi
May 27, 2003·Therapeutic Drug Monitoring·Kerstin Jönsson-VidesäterChrister Paul
Feb 1, 1991·International Journal of Radiation Oncology, Biology, Physics·P R TwentymanT Rhodes
May 15, 1994·International Journal of Radiation Oncology, Biology, Physics·X YiW Wang

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