Biomaterial Database

Altered ribonucleotide reductase activity in drug-resistant mammalian cells detected by an assay procedure for intact cells. 1980

S E Koropatnick, and J A Wright

Hydroxyurea, an antitumor drug which specifically inhibits ribonucleotide reductase, has been used as a selective agent to obtain single-step and double-step drug-resistant cell lines altered in reductase activity. Using an assay procedure developed for analyzing enzyme activity in intact cells a variety of novel changes in the properties of the enzyme activity was detected in the drug-resistant lines. Differences in cellular levels of enzyme activity, changes involving pyrimidine and purine substrate Km values, and altered enzyme sensitivity to hydroxyurea were found using the in vivo assay procedure. These changes could account for the drug-resistant phenotypes. The assay technique which is described in this report is easy to perform, can accurately determine enzyme activity in as few as 5 X 10(6) cells grown conveniently on the surface of a single tissue culture plate, and is a valuable quick screening method for identifying cells altered in different aspects of ribonucleotide reductase activity.

UI	MeSH Term	Description	Entries
D007739	L Cells	A cultured line of C3H mouse FIBROBLASTS that do not adhere to one another and do not express CADHERINS.	Earle's Strain L Cells,L Cell Line,L Cells (Cell Line),L-Cell Line,L-Cells,L-Cells, Cell Line,L929 Cell Line,L929 Cells,NCTC Clone 929 Cells,NCTC Clone 929 of Strain L Cells,Strain L Cells,Cell Line L-Cell,Cell Line L-Cells,Cell Line, L,Cell Line, L929,Cell Lines, L,Cell, L,Cell, L (Cell Line),Cell, L929,Cell, Strain L,Cells, L,Cells, L (Cell Line),Cells, L929,Cells, Strain L,L Cell,L Cell (Cell Line),L Cell Lines,L Cell, Strain,L Cells, Cell Line,L Cells, Strain,L-Cell,L-Cell Lines,L-Cell, Cell Line,L929 Cell,Strain L Cell
D008722	Methods	A series of steps taken in order to conduct research.	Techniques,Methodological Studies,Methodological Study,Procedures,Studies, Methodological,Study, Methodological,Method,Procedure,Technique
D009154	Mutation	Any detectable and heritable change in the genetic material that causes a change in the GENOTYPE and which is transmitted to daughter cells and to succeeding generations.	Mutations
D002460	Cell Line	Established cell cultures that have the potential to propagate indefinitely.	Cell Lines,Line, Cell,Lines, Cell
D004351	Drug Resistance	Diminished or failed response of an organism, disease or tissue to the intended effectiveness of a chemical or drug. It should be differentiated from DRUG TOLERANCE which is the progressive diminution of the susceptibility of a human or animal to the effects of a drug, as a result of continued administration.	Resistance, Drug
D006918	Hydroxyurea	An antineoplastic agent that inhibits DNA synthesis through the inhibition of ribonucleoside diphosphate reductase.	Hydroxycarbamid,Hydrea,Oncocarbide
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia
D012262	Ribonucleoside Diphosphate Reductase	An enzyme of the oxidoreductase class that catalyzes the formation of 2'-deoxyribonucleotides from the corresponding ribonucleotides using NADPH as the ultimate electron donor. The deoxyribonucleoside diphosphates are used in DNA synthesis. (From Dorland, 27th ed) EC 1.17.4.1.	UDP Reductase,Diphosphate Reductase, Ribonucleoside,Reductase, Ribonucleoside Diphosphate,Reductase, UDP
D012264	Ribonucleotide Reductases		Ribonucleotide Reductase,Reductase, Ribonucleotide,Reductases, Ribonucleotide
D051379	Mice	The common name for the genus Mus.	Mice, House,Mus,Mus musculus,Mice, Laboratory,Mouse,Mouse, House,Mouse, Laboratory,Mouse, Swiss,Mus domesticus,Mus musculus domesticus,Swiss Mice,House Mice,House Mouse,Laboratory Mice,Laboratory Mouse,Mice, Swiss,Swiss Mouse,domesticus, Mus musculus