Document Detail


Comparative effects of three nitrosourea derivatives on mammalian cell cycle progression.
MedLine Citation:
PMID:  1167349     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Three nitrosourea analogs, 1,3-bis(2-chloroethyl)-1-nitrosourea, 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea, and 1-trans-(2-chloroethyl)-3-cyclohexyl-1-(4-methylcyclohexyl)-1-nitrosourea, were examined for effects on survival and cell cycle traverse capacity in exponentially growing (cycling) populations of line CHO Chinese hamster cells and in cultures arrested in G1 by isoleucine deprivation during treatment with drugs, then returned to the cycling mode by restoration of isoleucine (noncycling cells). Among parameters studied were survival, cell division, DNA initiation capacities, cell cycle distributions, and rates of cell cycle traverse in drug-treated cycling and noncycling cells utilizing a protocol combining autoradiography, cell number enumeration, and flow microfluorometry. The results obtained were in generally good agreement with results obtained in vivo in other studies and included the following. Cells treated with any of these agents accumulated preferentially in late S and G2, primarily the result of a gross increase in duration of these phases of the cell cycle. There was also a prolongation of doubling time during the early stages following drug treatment and return to the proliferating mode of cells which ultimately survived. All three drugs induced mitotic nondisjunction in cells capable of dividing and also induced polyploidy by allowing multiple rounds of progression through the cell cycle in the absence of an intervening cell division. In treated populations, the G2-arrested and polyploid cells were among the first cells to die. Treated, noncycling cells that were returned to cycle exhibited a lower survival capacity than did treated, cycling cells. Finally, 1-(2-chloroethyl-3-cyclohexyl)-1-nitrosourea and 1-trans(2-chloroethyl)-3-(4-methylcyclohexyl)-1-nitrosourea induced a dramatic alteration in clonal morphology and growth patterns in surviving cells that persisted for at least a week after drug removal. The results obtained suggest that our model system may be useful as a predictive guide for determining response of susceptible tumor cells to treatment with chemotherapeutic agents.
Authors:
R A Tobey; H A Crissman
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Cancer research     Volume:  35     ISSN:  0008-5472     ISO Abbreviation:  Cancer Res.     Publication Date:  1975 Feb 
Date Detail:
Created Date:  1975-04-16     Completed Date:  1975-04-16     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  2984705R     Medline TA:  Cancer Res     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  460-70     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Animals
Antineoplastic Agents / pharmacology*
Autoradiography
Carmustine / pharmacology*
Cell Count
Cell Division / drug effects*
Cell Line
Cell Survival / drug effects
Cells, Cultured
Cricetinae
Cyclohexanes
DNA Replication / drug effects
Isoleucine
Mitosis / drug effects
Nitrosourea Compounds / pharmacology*
Polyploidy
Chemical
Reg. No./Substance:
0/Antineoplastic Agents; 0/Cyclohexanes; 0/Nitrosourea Compounds; 154-93-8/Carmustine; 73-32-5/Isoleucine

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


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