To increase the effectiveness of conventional radiotherapy in the treatment of cancer, different drugs can be administered. The aim of this project is to investigate biodegradable polyanhydride carrier matrices (PCPP-SA; 20:80) as a localized slow release delivery system for halogenated pyrimidines, in our case Bromodeoxyuridine (BrdU). Our in vitro experiments show that RIF-1 cells which have incorporated BrdU into their DNA over 4 doublings show significant increase in the initial slope (alpha-value) of their radiation cell survival curves, indicating an increase in radiosensitivity. To investigate the radiosensitization potential of BrdU in vivo, biodegradable BrdU/polymer combinations (20% w/w) were prepared and implanted directly into RIF-1 tumors, grown subcutaneously on the backs of C3H/Km mice. Clonogenic/excision assays were done with these tumors exposed to BrdU/polymer implants for several cell cycles before irradiation in situ to determine the extent of radiosensitization on the basis of cell survival. Tumor growth delay (TGD) measurements were also used as an index of tumor control following different treatments (single dose or fractionated doses) with and without the drug/polymer implants. All results indicate that BrdU, combined with radiation, increases TGD, while having no effect on non-irradiated tumors. The extent of substitution of thymidine by BrdU in DNA were also determined. This project was supported by the National Cancer Institute of Canada.
| Identifer | oai:union.ndltd.org:LACETR/oai:collectionscanada.gc.ca:QMM.20817 |
| Date | January 1997 |
| Creators | Doiron, Annie. |
| Publisher | McGill University |
| Source Sets | Library and Archives Canada ETDs Repository / Centre d'archives des thèses électroniques de Bibliothèque et Archives Canada |
| Language | English |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Format | application/pdf |
| Coverage | Master of Science (Department of Medical Radiation Physics.) |
| Rights | All items in eScholarship@McGill are protected by copyright with all rights reserved unless otherwise indicated. |
| Relation | alephsysno: 001604933, proquestno: MQ44160, Theses scanned by UMI/ProQuest. |
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