Physiological mechanisms of radiation sensitization by pentoxifylline.
The aim of this study was to investigate whether multiple injections (daily for 5 days) of the hemorheological agent pentoxifylline (PTX) affected tumor physiological parameters (i.e., tumor pO2, tumor pH, and tumor interstitial fluid pressure) during the tumor growth of FSaII murine fibrosarcoma in C3H mice. The radiation sensitization by multiple injections of PTX (daily for 5 days) was also studied. Following multiple administrations of PTX, PTX significantly improved tumor oxygenation in all sizes of tumors tested. Our results showed that the elevated tumor interstitial fluid pressure (TIFP) in solid tumors could be reduced by PTX. Based on our results with the improvement in tumor pathophysiology, PTX may be of use during tumor therapies in which the outcome may be detrimentally affected by the presence of hypoxia. As anticipated, multiple injections of PTX with fractionated x-irradiation prolonged the radiation-induced growth delay in FSaII tumors, producing an enhancement ratio of 1.8 of the growth delay at 15 days. However, we did not observe any alteration in cellular oxygen consumption (QO2) after the treatment with PTX. Therefore, we concluded that PTX-induced radiosensitization was due to an increase in tumor pO2, not a reduction in QO2.
Lee
I
I
Department of Radiation Oncology, University of Pennsylvania School of Medicine, Philadelphia, PA 19104-6072, USA. ilee@pcyc.com
Biaglow
J E
JE
Lee
J
J
Cho
M J
MJ
D000818:Animals; D015687:Cell Hypoxia / Q000187:drug effects* / Q000528:radiation effects; D004907:Erythrocyte Deformability / Q000187:drug effects; D004912:Erythrocytes / Q000187:drug effects / Q000502:physiology; D005110:Extracellular Space / Q000187:drug effects* / Q000502:physiology; D005260:Female; D005354:Fibrosarcoma / Q000098:blood supply / Q000503:physiopathology* / Q000532:radiotherapy; D006401:Hematologic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D006863:Hydrogen-Ion Concentration / Q000187:drug effects; D051379:Mice; D008809:Mice, Inbred C3H; D010101:Oxygen Consumption / Q000187:drug effects* / Q000528:radiation effects; D010431:Pentoxifylline / Q000008:administration & dosage / Q000494:pharmacology*; D011836:Radiation Tolerance / Q000187:drug effects; D011837:Radiation-Protective Agents / Q000008:administration & dosage / Q000494:pharmacology*; D011879:Radiotherapy Dosage
D006401:Hematologic Agents; D011837:Radiation-Protective Agents; D010431:Pentoxifylline