title: Tumoricidal activity of low-energy 160-KV versus 6-MV X-rays against platinum-sensitized F98 glioma cells.
abstract: 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 µg/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 µg/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.
authors.affiliation: Biophysics Graduate Program, The Ohio State University, 113 Biological Sciences Building, 484 W 12th Avenue, Columbus, OH 43210, USA.
authors.forename: Sara N
authors.initials: SN
authors.lastname: Lim
authors.affiliation: Biophysics Graduate Program, The Ohio State University, 113 Biological Sciences Building, 484 W 12th Avenue, Columbus, OH 43210, USA Department of Astronomy, The Ohio State University, 4055 McPherson Laboratory, 140 W 18th Avenue, Columbus, OH 43210, USA pradhan.1@osu.edu.
authors.forename: Anil K
authors.initials: AK
authors.lastname: Pradhan
authors.affiliation: Department of Pathology, The Ohio State University, 4132 Graves Hall, 333 West 10th Avenue, Columbus, OH 43210, USA rolf.barth@osumc.edu.
authors.forename: Rolf F
authors.initials: RF
authors.lastname: Barth
authors.affiliation: Department of Astronomy, The Ohio State University, 4055 McPherson Laboratory, 140 W 18th Avenue, Columbus, OH 43210, USA.
authors.forename: Sultana N
authors.initials: SN
authors.lastname: Nahar
authors.affiliation: Department of Pathology, The Ohio State University, 4132 Graves Hall, 333 West 10th Avenue, Columbus, OH 43210, USA.
authors.forename: Robin J
authors.initials: RJ
authors.lastname: Nakkula
authors.affiliation: Department of Pathology, The Ohio State University, 4132 Graves Hall, 333 West 10th Avenue, Columbus, OH 43210, USA.
authors.forename: Weilian
authors.initials: W
authors.lastname: Yang
authors.affiliation: Department of Chemistry and Biochemistry, The Ohio State University, Newman & Wolfrom Laboratory, 100 W 18th Avenue, OH 43210, USA.
authors.forename: Alycia M
authors.initials: AM
authors.lastname: Palmer
authors.affiliation: Department of Chemistry and Biochemistry, The Ohio State University, Newman & Wolfrom Laboratory, 100 W 18th Avenue, OH 43210, USA.
authors.forename: Claudia
authors.initials: C
authors.lastname: Turro
authors.affiliation: Department of Radiation Oncology, The Ohio State University, 300 W 10th Avenue, Columbus, OH 43210, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Weldon
authors.affiliation: Department of Radiation Oncology, The Ohio State University, 300 W 10th Avenue, Columbus, OH 43210, USA.
authors.forename: Erica Hlavin
authors.initials: EH
authors.lastname: Bell
authors.affiliation: Center for Biostatistics, The Ohio State University, 2012 Kenny Road, Columbus, OH 43210, USA.
authors.forename: Xiaokui
authors.initials: X
authors.lastname: Mo
mesh_terms: D065638:Absorption, Radiation; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage; D017209:Apoptosis / Q000528:radiation effects*; D016190:Carboplatin / Q000008:administration & dosage*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000528:radiation effects; D003198:Computer Simulation; D004307:Dose-Response Relationship, Radiation; D051379:Mice; D008954:Models, Biological; D015233:Models, Statistical; D009374:Neoplasms, Experimental / Q000473:pathology* / Q000532:radiotherapy*; D010315:Particle Accelerators; D011829:Radiation Dosage; D011838:Radiation-Sensitizing Agents / Q000008:administration & dosage; D011882:Radiotherapy, High-Energy / Q000379:methods*; D051381:Rats; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D011838:Radiation-Sensitizing Agents; D016190:Carboplatin
keywords: B16 murine melanoma; F98 rat glioma; comparison of 160-kV vs 6-MV X-rays; dose enhancement factor; platinum radiosensitization