Examination of Bystander Cell Death Following Low-LET Irradiation

Abstract

<p>This thesis describes an analysis of the influence of dose and dose rate from low LET radiation on the induction of a cytotoxic bystander effect. The general direction was as follows:</p> <p>a) Utilize a well – established reporter cell line with two types of low – LET radiation across varying dose and dose rates in order to assess the possibility of a dose rate effect. These results identified the recovery of bystander cell survival to control levels after high dose treatment. Additionally, dose rate effects were seen at high dose treatments following electron irradiation as well as between similar low – LET sources.</p> <p>b) Apply aggressive radiation treatment for toxic medium production in order to elicit a bystander cell death response in a cell line with no previous observed effect. Results indicated a similar response to a reporter line including an increase in cell survival at high doses. Transforming growth factor β1 (TGF-β1) was identified as necessary to the observed effect.</p> <p>c) Develop a dosimetry model for <em>in vitro</em> bystander studies following toxic medium production with a β-emitting radiopharmaceutical. Furthermore, use this model to re-examine survival fraction data in comparison with traditional external beam treatment. A code-base and application were developed. Comparison between treatments indicated a similar survival curve shape with differences in the magnitude of the response. This is possibly the result of cell response to low – dose rates from radiopharmaceutical treatment.</p> <p>The overall conclusion points to the importance of dose rate in observed bystander cell death as well as the differentiating response at high doses. Additionally, the similarity in survival curve behaviour across differing cell type's further points to common underlying critical mechanisms. However, it is believed that further data acquisition and aggregation is required in order to build a robust model for the influence of these factors.</p>