Alterations in the components of ribonucleotide reductase in hydroxyurea-resistant hamster cells.
Two components of mammalian ribonucleotide reductase have been separated by blue dextran-Sepharose chromatography from a hydroxyurea-resistant cell line, NCR-30A2, and its parental wild type. Analysis of reductase activity in these cells and the enzyme components reveals that there are three alterations involving ribonucleotide reductase activity in NCR-30A2 cells. There is an elevation in the effector-binding (EB) component, an elevation in the non-heme-iron-containing (NHI) component, and an alteration in the NHI component that renders the enzyme less sensitive to inhibition by hydroxyurea. These findings easily account for the resistance of NCR-30A2 cells to the antitumor agent hydroxyurea, and to other drugs with a similar mode of action.
D000818:Animals; D002460:Cell Line; D002850:Chromatography, Gel; D006224:Cricetinae; D004351:Drug Resistance; D005260:Female; D006918:Hydroxyurea / Q000494:pharmacology*; D046911:Macromolecular Substances; D010053:Ovary / Q000187:drug effects / Q000201:enzymology; D012262:Ribonucleoside Diphosphate Reductase / Q000378:metabolism; D012264:Ribonucleotide Reductases / Q000032:analysis*
D046911:Macromolecular Substances; C019857:CDP reductase; D012264:Ribonucleotide Reductases; D012262:Ribonucleoside Diphosphate Reductase; D006918:Hydroxyurea