Document Detail


Significance of manipulating tumour hypoxia and radiation dose rate in terms of local tumour response and lung metastatic potential, referring to the response of quiescent cell populations.
MedLine Citation:
PMID:  20739345     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The purpose of this study was to evaluate the influence of manipulating intratumour oxygenation status and radiation dose rate on local tumour response and lung metastases following radiotherapy, referring to the response of quiescent cell populations within irradiated tumours. B16-BL6 melanoma tumour-bearing C57BL/6 mice were continuously given 5-bromo-2'-deoxyuridine (BrdU) to label all proliferating (P) cells. They received gamma-ray irradiation at high dose rate (HDR) or reduced dose rate (RDR) following treatment with the acute hypoxia-releasing agent nicotinamide or local hyperthermia at mild temperatures (MTH). Immediately after the irradiation, cells from some tumours were isolated and incubated with a cytokinesis blocker. The responses of the quiescent (Q) and total (proliferating + Q) cell populations were assessed based on the frequency of micronuclei using immunofluorescence staining for BrdU. In other tumour-bearing mice, 17 days after irradiation, macroscopic lung metastases were enumerated. Following HDR irradiation, nicotinamide and MTH enhanced the sensitivity of the total and Q-cell populations, respectively. The decrease in sensitivity at RDR irradiation compared with HDR irradiation was slightly inhibited by MTH, especially in Q cells. Without gamma-ray irradiation, nicotinamide treatment tended to reduce the number of lung metastases. With gamma-rays, in combination with nicotinamide or MTH, especially the former, HDR irradiation decreased the number of metastases more remarkably than RDR irradiation. Manipulating both tumour hypoxia and irradiation dose rate have the potential to influence lung metastasis. The combination with the acute hypoxia-releasing agent nicotinamide may be more promising in HDR than RDR irradiation in terms of reducing the number of lung metastases.
Authors:
S Masunaga; Y Matsumoto; G Kashino; R Hirayama; Y Liu; H Tanaka; Y Sakurai; M Suzuki; Y Kinashi; A Maruhashi; K Ono
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  The British journal of radiology     Volume:  83     ISSN:  1748-880X     ISO Abbreviation:  Br J Radiol     Publication Date:  2010 Sep 
Date Detail:
Created Date:  2010-08-26     Completed Date:  2011-02-03     Revised Date:  2013-03-07    
Medline Journal Info:
Nlm Unique ID:  0373125     Medline TA:  Br J Radiol     Country:  England    
Other Details:
Languages:  eng     Pagination:  776-84     Citation Subset:  AIM; IM    
Affiliation:
Particle Radiation Oncology Research Center, Research Reactor Institute, Kyoto University, Osaka, Japan. smasuna@rri.kyoto-u.ac.jp
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MeSH Terms
Descriptor/Qualifier:
Animals
Bromodeoxyuridine / administration & dosage,  diagnostic use
Cell Hypoxia / drug effects,  radiation effects*
Combined Modality Therapy
Female
Gamma Rays / therapeutic use
Lung Neoplasms / secondary*
Melanoma, Experimental / metabolism,  radiotherapy*,  secondary*
Mice
Mice, Inbred C57BL
Niacinamide / administration & dosage*
Radiotherapy Dosage
Temperature
Tumor Cells, Cultured
Chemical
Reg. No./Substance:
59-14-3/Bromodeoxyuridine; 98-92-0/Niacinamide
Comments/Corrections

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