Journal
JOURNAL OF RADIATION RESEARCH
Volume 56, Issue 1, Pages 77-89Publisher
OXFORD UNIV PRESS
DOI: 10.1093/jrr/rru084
Keywords
comparison of 160-kV vs 6-MV X-rays; platinum radiosensitization; F98 rat glioma; B16 murine melanoma; dose enhancement factor
Funding
- Ohio State University
- Voices Against Brain Cancer
- Kevin J. Mullin Memorial Fund for Brain Tumor Research
- Departments of Pathology, Chemistry and Astronomy of The Ohio State University
- Direct For Mathematical & Physical Scien
- Division Of Astronomical Sciences [1312441] Funding Source: National Science Foundation
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The purposes of this study were (i) to investigate the differences in effects between 160-kV low-energy and 6-MV high-energy X-rays, both by computational analysis and in vitro studies; (ii) to determine the effects of each on platinum-sensitized F98 rat glioma and murine B16 melanoma cells; and (iii) to describe the in vitro cytotoxicity and in vivo toxicity of a Pt(II) terpyridine platinum (Typ-Pt) complex. Simulations were performed using the Monte Carlo code Geant4 to determine enhancement in absorption of low-versus high-energy X-rays by Pt and to determine dose enhancement factors (DEFs) for a Pt-sensitized tumor phantom. In vitro studies were carried out using Typ-Pt and again with carboplatin due to the unexpected in vivo toxicity of Typ-Pt. Cell survival was determined using clonogenic assays. In agreement with computations and simulations, in vitro data showed up to one log unit reduction in surviving fractions (SFs) of cells treated with 1-4 mu g/ml of Typ-Pt and irradiated with 160-kV versus 6-MV X-rays. DEFs showed radiosensitization in the 50-200 keV range, which fell to approximate unity at higher energies, suggesting marginal interactions at MeV energies. Cells sensitized with 1-5 or 7 mu g/ml of carboplatin and then irradiated also showed a significant decrease (P < 0.05) in SFs. However, it was unlikely this was due to increased interactions. Theoretical and in vitro studies presented here demonstrated that the tumoricidal activity of low-energy X-rays was greater than that of high-energy X-rays against Pt-sensitized tumor cells. Determining whether radiosensitization is a function of increased interactions will require additional studies.
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