Document Detail

Potentiation of 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea's toxicity in vitro by two new bioreductive agents.
MedLine Citation:
PMID:  1399828     Owner:  NLM     Status:  MEDLINE    
Two new bioreductive compounds, 9-[3-(2-nitro-1-imidazolyl)propylamino]acridine hydrochloride (NLA-1) and 9-[2-(2-nitro-1-imidazolyl)ethylamino]acridine hydrochloride (NLA-2), which behave as hypoxic cytotoxins and radiosensitizers, have been investigated for potentiation of 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea's (CCNU) cytotoxic activity in vitro using V-79 cells. The preincubation effect as well as conditions of coadministration of CCNU with each sensitizer have been examined. In this latter case, the median-effect analysis was applied to evaluate whether the phenomenon was additive or synergistic. A clonogenic assay was used to score survival. Both bioreductive compounds, even at very low concentrations, significantly enhance the cytotoxic activity of CCNU under conditions of hypoxic preincubation. The enhancement of CCNU cytotoxicity is dependent upon preincubation time and the concentrations of both CCNU and the specific bioreductive agent. Coincubation of cells under hypoxia with CCNU and each bioreductive agent led to some potentiation, but only at lower survival levels. No chemosensitization was observed under aerobic conditions with either sensitizer.
M V Papadopoulou; A Mainwaring; W D Bloomer
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Japanese journal of cancer research : Gann     Volume:  83     ISSN:  0910-5050     ISO Abbreviation:  Jpn. J. Cancer Res.     Publication Date:  1992 Aug 
Date Detail:
Created Date:  1992-11-03     Completed Date:  1992-11-03     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  8509412     Medline TA:  Jpn J Cancer Res     Country:  JAPAN    
Other Details:
Languages:  eng     Pagination:  907-13     Citation Subset:  IM    
Department of Radiation Oncology, University of Pittsburgh, PA 15213.
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MeSH Terms
Aminoacridines / pharmacology,  toxicity*
Cell Line
Cell Survival / drug effects*
Chelating Agents / pharmacology,  toxicity*
Dose-Response Relationship, Drug
Drug Synergism
Lomustine / pharmacology,  toxicity*
Nitroimidazoles / pharmacology,  toxicity*
Radiation-Sensitizing Agents / pharmacology,  toxicity*
Reg. No./Substance:
0/Aminoacridines; 0/Chelating Agents; 0/Nitroimidazoles; 0/Radiation-Sensitizing Agents; 13010-47-4/Lomustine; 140448-36-8/NLA 1; 142618-00-6/9-(2-(2-nitro-1-imidazolyl)ethylamino)acridine

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

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