Document Detail


Metabolism and action of benzamide riboside in Chinese hamster ovary cells.
MedLine Citation:
PMID:  8742104     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Benzamide riboside (3-(1-deoxy-beta-D-ribofuranosyl)benzamide, BR) a new analog of nicotinamide riboside, is toxic to Chinese hamster ovary cells and inhibits guanine nucleotide synthesis in a manner comparable to that of tiazofurin (2-beta-D-ribofuranosylthiazole-4-carboxamide). Adenosine kinase deficient cells demonstrate slight resistance but retain the ability to form the NAD analog, benzamide adenine dinucleotide (BAD). HPLC analysis of BAD containing cells is described. A BR resistant cell line was isolated that demonstrates cross-resistance to both tiazofurin and 6-aminonicotinamide, suggesting a common metabolic step; enzymatic analysis indicates reduced levels of NAD pyrophosphorylase in these cells. BR toxicity was only partially reversed or prevented by the presence of guanosine, suggesting either that BR inhibits guanine salvage to some extent or, more probably, that BR can, at high concentration, inhibit cell growth by another mechanism in addition to inhibition of guanine nucleotide synthesis. Cells incubated with BR for several hours retain the ability to salvage exogenously provided guanosine. The demonstration that BAD can be phosphorylated by NAD kinase, presumably to form BADP, suggests that this metabolite may be formed in cells and may have inhibitory activity at high concentrations of BR.
Authors:
P P Saunders; S Arimilli; K Krohn; M A Muhs; E Alvarez; R Surve-lyer
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Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Anti-cancer drugs     Volume:  7     ISSN:  0959-4973     ISO Abbreviation:  Anticancer Drugs     Publication Date:  1996 Jan 
Date Detail:
Created Date:  1996-11-14     Completed Date:  1996-11-14     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  9100823     Medline TA:  Anticancer Drugs     Country:  ENGLAND    
Other Details:
Languages:  eng     Pagination:  93-9     Citation Subset:  IM    
Affiliation:
Department of Clinical Investigation, The University of Texas MD Anderson Cancer Center, Houston 77030, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Antineoplastic Agents / metabolism,  pharmacology
CHO Cells / drug effects,  metabolism
Cricetinae
Drug Resistance
Enzyme Inhibitors / metabolism*,  pharmacology
NAD / metabolism
Nucleosides / metabolism*,  pharmacology
Phosphorylation
Ribavirin / analogs & derivatives,  metabolism,  pharmacology
Grant Support
ID/Acronym/Agency:
CA 48945/CA/NCI NIH HHS
Chemical
Reg. No./Substance:
0/Antineoplastic Agents; 0/Enzyme Inhibitors; 0/Nucleosides; 138385-29-2/3-(1-deoxyribofuranosyl)benzamide; 36791-04-5/Ribavirin; 53-84-9/NAD; 60084-10-8/tiazofurin

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