Document Detail

Exploitation of hypoxia for radiation therapy: a lesson from phenothiazines.
MedLine Citation:
PMID:  8869925     Owner:  NLM     Status:  MEDLINE    
In experimental radiation therapy of tumours, phenothiazines are known to sensitize hypoxic cancer cells while offering protection to the normal surrounding tissue. It is hypothesized that the differential radiosensitization of tumour cells and radioprotection of normal cells by phenothiazines is related to the presence of Fe2+ and Fe3+ ion concentration respectively. As a result of changed biochemical environment such as pH, hypoxia and accumulation of ferritin, the Fe2+ ion concentration in tumours, especially in the hypoxic cells, is expected to be higher (and to be further enhanced by irradiation) than in the well-oxygenated normal cells. In normal cells, iron would predominantly be in the Fe3+ form, which might increase the protective effect of phenothiazines. A many-fold increase in radiation effect has been shown by us in vivo as well as in vitro systems in the combined presence of phenothiazines and Fe2+ ions. Our findings suggest that the hypoxic condition can be exploited for radiation therapy by employing suitable metal-based chemomodulation.
R K Kale
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Medical hypotheses     Volume:  47     ISSN:  0306-9877     ISO Abbreviation:  Med. Hypotheses     Publication Date:  1996 Aug 
Date Detail:
Created Date:  1997-01-22     Completed Date:  1997-01-22     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  7505668     Medline TA:  Med Hypotheses     Country:  ENGLAND    
Other Details:
Languages:  eng     Pagination:  107-10     Citation Subset:  IM    
Radiation Biology Laboratory, School of Life Sciences, Jawaharlal Nehru University, New Delhi, India.
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MeSH Terms
Ferritins / metabolism
Hydroxyl Radical
Iron / metabolism
Lipid Peroxidation / radiation effects
Microsomes, Liver / metabolism,  radiation effects
Neoplasms / radiotherapy
Neoplasms, Experimental / physiopathology,  radiotherapy*
Phenothiazines / therapeutic use*
Radiation-Protective Agents / therapeutic use*
Radiation-Sensitizing Agents / therapeutic use*
Radiotherapy / methods*
Reg. No./Substance:
0/Phenothiazines; 0/Radiation-Protective Agents; 0/Radiation-Sensitizing Agents; 3352-57-6/Hydroxyl Radical; 7439-89-6/Iron; 9007-73-2/Ferritins

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