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Antioxidants 2017, 6(3), 58; doi:10.3390/antiox6030058

High Dose Ascorbate Causes Both Genotoxic and Metabolic Stress in Glioma Cells

1
School of Biological Sciences, Victoria University, P.O.Box 600, Wellington 6140, New Zealand
2
Malaghan Institute of Medical Research, P.O.Box 7060, Wellington 6242, New Zealand
3
Department of Radiation Therapy, University of Otago, P.O.Box 7343, Wellington 6242, New Zealand
*
Author to whom correspondence should be addressed.
Received: 10 May 2017 / Revised: 30 June 2017 / Accepted: 19 July 2017 / Published: 22 July 2017
(This article belongs to the Special Issue Vitamin C: Current Concepts in Human Physiology)
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Abstract

We have previously shown that exposure to high dose ascorbate causes double stranded breaks (DSBs) and a build-up in S-phase in glioblastoma (GBM) cell lines. Here we investigated whether or not this was due to genotoxic stress as well as metabolic stress generated by exposure to high dose ascorbate, radiation, ascorbate plus radiation and H2O2 in established and primary GBM cell lines. Genotoxic stress was measured as phosphorylation of the variant histone protein, H2AX, 8-oxo-7,8-dihydroguanine (8OH-dG) positive cells and cells with comet tails. Metabolic stress was measured as a decrease in NADH flux, mitochondrial membrane potential (by CMXRos), ATP levels (by ATP luminescence) and mitochondrial superoxide production (by mitoSOX). High dose ascorbate, ascorbate plus radiation, and H2O2 treatments induced both genotoxic and metabolic stress. Exposure to high dose ascorbate blocked DNA synthesis in both DNA damaged and undamaged cell of ascorbate sensitive GBM cell lines. H2O2 treatment blocked DNA synthesis in all cell lines with and without DNA damage. DNA synthesis arrest in cells with damaged DNA is likely due to both genotoxic and metabolic stress. However, arrest in DNA synthesis in cells with undamaged DNA is likely due to oxidative damage to components of the mitochondrial energy metabolism pathway. View Full-Text
Keywords: high dose ascorbate; H2O2; radiation; oxidative stress; genotoxic stress; metabolic stress; DNA synthesis arrest high dose ascorbate; H2O2; radiation; oxidative stress; genotoxic stress; metabolic stress; DNA synthesis arrest
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MDPI and ACS Style

Castro, M.L.; Carson, G.M.; McConnell, M.J.; Herst, P.M. High Dose Ascorbate Causes Both Genotoxic and Metabolic Stress in Glioma Cells. Antioxidants 2017, 6, 58.

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