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The Two Faces of Ascorbate: Prooxidant Activity and Radio-Sensitisation

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Version 2 2023-09-25, 02:07
Version 1 2021-11-15, 18:02
thesis
posted on 2023-09-25, 02:07 authored by Georgia Carson

Although not recommended by mainstream oncologists, intravenous injections of pharmacological ascorbate are currently an alternative therapy option for cancer patients. Research has not yet determined whether high-dose ascorbate interacts favourably with radiation therapy to increase DNA damage, and therefore cell death in cancer. Some studies suggest that ascorbate can act as a prooxidant and increase the cytotoxic effect of irradiation in vitro. Glioblastoma multiforme (GBM) is a primary brain astrocytoma that is highly therapy resistant, so patients would be advantaged if ascorbate radiosensitised their cancer.  In this investigation, flow cytometry and single cell gel electrophoresis (comet tail assay) were used to measure three indicators of DNA damage in GBM cells in response to ascorbate and irradiation, and were contrasted with immunofluorescence-revealed DNA damage from an intracranial mouse model of GBM.   The pro-oxidant, radiosensitisation role of ascorbate was confirmed, as measured by H2AX, 8OHdG, and DSBs in vitro. With all three of these markers of DNA damage, combinations of irradiation and ascorbate had increased damage compared with individual treatments. However preliminary in vivo evidence indicates that increased DNA damage did not occur in an animal model of GBM, and in fact ascorbate may protect from DNA damage in an in vivo context.  These findings complement previous results from our lab, and serve to fill in gaps in knowledge specifically around the DNA damaging effects of ascorbate. The unique nature of the brain environment, as enclosed by the blood brain barrier, prevents translation of data from other non-brain cancer studies, as such, this investigation also contributes to the exploration of a much needed avenue of research. Considering the context of ascorbate treatment as a potentially harmful currently used adjuvant, it is imperative to confirm or disprove its efficacy in a clinically relevant environment.

History

Copyright Date

2016-01-01

Date of Award

2016-01-01

Publisher

Te Herenga Waka—Victoria University of Wellington

Rights License

CC BY-SA 4.0

Degree Discipline

Cell and Molecular Bioscience

Degree Grantor

Te Herenga Waka—Victoria University of Wellington

Degree Level

Masters

Degree Name

Master of Science

Victoria University of Wellington Unit

Malaghan Institute for Medical Research

ANZSRC Type Of Activity code

1 PURE BASIC RESEARCH

Victoria University of Wellington Item Type

Awarded Research Masters Thesis

Language

en_NZ

Victoria University of Wellington School

School of Biological Sciences

Advisors

McConnell, Melanie