Abstract
The role of vitamin C (ascorbate) in cancer treatment is unresolved, with some studies showing it to have a radio-sensitising effect on tumour cells but others associating it with treatment resistance. Furthermore, many cancer patients have reduced plasma ascorbate. Ascorbate status of cancer patients undergoing radiation therapy, however, is unreported. This study aimed to measure ascorbate status of patients undergoing radiation therapy for cancer and determine associations with patient or tumour characteristics. This study also explored the interaction of ascorbate and radiation in vitro. Patients undergoing radiation therapy for cancer at Christchurch hospital were consented to provide blood samples and complete a simple questionnaire. Samples were taken prior to their first and post their fifth fraction of ionizing radiation. Healthy controls provided a single blood sample. Plasma ascorbate was measured using high-performance liquid chromatography. Concentrations were compared between first and second measurements and clinicopathological characteristics (tumour type, grade, patient age, smoking status and exercise habits, 24-hour dietary intake of ascorbate). Data was statistically analysed using student’s t-tests and Pearson correlations. Additionally, glioblastoma cells (U87, U251) and clones (U87 3.19, U251 1.8) genetically modified to lack functioning sodium vitamin C transporters, were treated with ascorbate (200 and 500µM) and irradiated (0.5, 2, and 10 Gy) using a linear accelerator at Christchurch hospital. Cells were assessed for viability (metabolic activity) and cell cycle analysis (flow cytometry). Plasma ascorbate was presented for fasting participants (consumed <45mg ascorbate on the day of venepuncture). There was no significant change in plasma ascorbate of fasting patients (n=28) following five doses of radiation, nor any significant difference in status compared to healthy controls (n=10) (p>0.05). When classified according to international guidelines, most patients had either adequate (32%) or saturating (27%) levels of plasma ascorbate. Only one patient in the cohort was considered deficient. Ascorbate was weakly correlated with 24-hour dietary intake of ascorbate. In vitro, there was no difference in cell viability, between non-radiated and radiated cells regardless of ascorbate treatment (p>0.05). Flow cytometry showed disruption of the cell cycle following radiation, though the impact of ascorbate treatment was not determined. Patient data showed no evidence of reduction in plasma ascorbate due to cancer or radiation therapy. Cell studies demonstrated feasibility of using high-energy linear accelerator for in vitro research. Further studies will confirm cell response to radiation in combination with ascorbate treatment.