Document Detail

Survival in subpopulations of cells derived from solid KHT sarcomas by centrifugal elutriation following treatment with CCNU and MISO.
MedLine Citation:
PMID:  6480449     Owner:  NLM     Status:  MEDLINE    
Misonidazole (MISO) has been shown to enhance the cytotoxicity of 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea (CCNU) in a number of different animal tumor systems. We have investigated the response to therapy of the various subpopulations of cells comprising the KHT sarcoma, to determine whether chemopotentiation occurred as a preferential enhancement of killing in one subpopulation of cells. Twenty-four hr after drug treatment, cells dissociated from solid tumors were separated into homogeneous populations based on cell size by the technique of centrifugal elutriation. By this method the majority of the non-neoplastic cells could be removed and the tumor cells separated into fractions containing 90 to 95% G1 cells, 70 to 75% S cells and 70 to 80% G2M cells. Clonogenic cell survival was measured for each elutriated fraction. In vivo treatment with 0.5 mg/g MISO produced no measurable cell-kill across the cell cycle. Those cells in late G1 and S phase 24 hr after treatment were most sensitive to CCNU alone. The enhancement of CCNU cytotoxicity by MISO occurred primarily in the early G1 and S fractions. These data suggest that chemopotentiation does not occur equally in all tumor cell subpopulations and that some specificity of enhanced cell killing exists.
S A Hill; P C Keng; D W Siemann
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Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  International journal of radiation oncology, biology, physics     Volume:  10     ISSN:  0360-3016     ISO Abbreviation:  Int. J. Radiat. Oncol. Biol. Phys.     Publication Date:  1984 Sep 
Date Detail:
Created Date:  1984-11-16     Completed Date:  1984-11-16     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  7603616     Medline TA:  Int J Radiat Oncol Biol Phys     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  1615-8     Citation Subset:  IM    
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MeSH Terms
Cell Cycle
Cell Separation
Cell Survival / drug effects
Drug Synergism
Drug Therapy, Combination
Flow Cytometry
Lomustine / therapeutic use*
Mice, Inbred C3H
Misonidazole / therapeutic use*
Neoplasm Transplantation
Nitroimidazoles / therapeutic use*
Radiation-Sensitizing Agents / therapeutic use
Sarcoma, Experimental / drug therapy*
Grant Support
Reg. No./Substance:
0/Nitroimidazoles; 0/Radiation-Sensitizing Agents; 13010-47-4/Lomustine; 13551-87-6/Misonidazole

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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