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

Antioxidants

Patries M. Herst¹  Maria Leticia Castro²  Georgia M. Carson²  Melanie J. McConnell² 

[1] Malaghan Institute of Medical Research, P.O.Box 7060, Wellington 6242, New Zealand;School of Biological Sciences, Victoria University, P.O.Box 600, Wellington 6140, New Zealand;

关键词: high dose ascorbate;    H2O2;    radiation;    oxidative stress;    genotoxic stress;    metabolic stress;    DNA synthesis arrest;   

DOI  :  10.3390/antiox6030058

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown