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Biochemical changes and cytotoxicity associated with methionine depletion in paediatric central nervous system tumour cell lines

Najim, N, Podmore, I, Mcgown, A and Estlin, E 2009, 'Biochemical changes and cytotoxicity associated with methionine depletion in paediatric central nervous system tumour cell lines' , Anticancer Research, 29 (8) , pp. 2971-2976.

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Abstract

The aim of this study was to investigate the importance of the extent and duration of methionine depletion as a cause of cytotoxicity for CNS tumour cell lines, and also to investigate the associated in vitro cellular biochemical responses. MATERIALS AND METHODS: Cell growth inhibition was assayed by the SRB assay. Intracellular methionine levels were measured by GC/MS following dervatization with MTBSTFA. After methionine depletion, methionine synthase and MGMT activities were also determined. Glutathione levels were assayed by HPLC after derivatization with OPA. RESULTS: Medulloblastoma (Daoy) and glioma (D54) cells were found to be methionine dependent and effects on proliferation, apoptosis and clonogenic survival were dependent on time and degree of methionine depletion. Methionine depletion also caused a demonstrable decrease in L-methionine levels and an increase in glutathione levels for both cell lines, with a decrease in MGMT activity for Daoy cells. CONCLUSION: Daoy and D54 cells are methionine dependent; the degree and duration of methionine depletion is related to cell death. The associated biochemical changes in MGMT and glutathione may be expected to modulate chemosensitivity and this will be investigated in future studies.

Item Type: Article
Themes: Subjects / Themes > R Medicine > RS Pharmacy and materia medica
Subjects / Themes > R Medicine > RC Internal medicine > RC0254 Neoplasms. Tumors. Oncology (including Cancer)
Health and Wellbeing
Schools: Colleges and Schools > College of Science & Technology
Colleges and Schools > College of Science & Technology > School of Environment and Life Sciences
Colleges and Schools > College of Science & Technology > School of Environment and Life Sciences > Biomedical Research Centre
Journal or Publication Title: Anticancer Research
Publisher: International Institute of Anticancer Research (IIAR)
Refereed: Yes
ISSN: 0250-7005
Funders: Kidscan
Depositing User: AT McGown
Date Deposited: 16 Mar 2010 13:41
Last Modified: 30 Jul 2014 11:10
URI: http://usir.salford.ac.uk/id/eprint/3299

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