Investigation of manganese as a radioprotective agent in human cancers
- Publication Type:
- Thesis
- Issue Date:
- 2022
Open Access
Copyright Clearance Process
- Recently Added
- In Progress
- Open Access
This item is open access.
Manganese complexes are effective and catalytic scavenges of O2• – , mimicking the behaviour of super-oxide dismutase. Recently, manganese concentrations were shown to correlate with inferred radiotherapy resistance in human tumours. Radiation plays an important role in the treatment of cancer, but there is no reliable way to predict a tumour’s response to therapy. Imaging of manganese using laser ablation–inductively coupled plasma–mass spectrometry (LA–ICP–MS) could provide a novel way of predicting radioresistance and informing treatments, but current methods have significant shortcomings. This thesis addresses these shortcomings by developing low-background standards and open-source single-cell (sc) and LA–ICP–MS software. These new tools are used to interrogate the metal contents of skin, testis, pancreas and brain tumours. Radioresistance was also investigated in a breast cancer cell model using ultraviolet (UV) radiation as a gamma surrogate.
Moulds were used to reproducibly prepare gelatine standards with controllable thickness and improved surface characteristics. Background signals for transition metals were reduced by removing endogenous elements from the gelatine using chelating resins.
Open-source LA–ICP–MS imaging software was created using modern design and visualisation philosophies, minimising errors in data interpretation.
Transition metals were quantified in testis, skin and pancreatic cancer. Concentrations of Mn, Fe, Cu and Zn all correlated with the inferred resistance of tumours. In testis tumours with different inferred radiosensitivities, only Cu correlated with resistance.
Metals were quantified in glioblastoma and meningioma, brain tumours with vastly different patient outcomes. Glioblastoma contained significantly more Cu than benign meningioma. Concentrations of Mn were increased in grade II over grade I meningioma, but did not reach significance.
To aid in the investigation of single-cellular Mn concentrations software was developed for single-particle (sp) and scICP–MS analysis. The software was demonstrated using the analysis of TiO2 nanoparticles in water, LA–spICP–MS of micro-plastics in soil and the measurement of C fixation in algae.
The radioprotective properties of Mn2+ were investigated using UV radiation and a breast cancer cell model. Similar viabilities were observed across the range of treatments; Mn had no protective effects. Multi-modal distributions of Mn in was observed in treated cells using scICP–MS, information that was lost when digestion was performed.
The tools created during this thesis will assist in future investigations of manganese and radio-resistance. Further experiments with large sample sizes and radiotherapy patient outcomes are required to definitively conclude if manganese complexes contribute to tumour radioresistance.
Please use this identifier to cite or link to this item: