Bromodeoxyuridine mutagenesis, ribonucleotide reductase activity, and deoxyribonucleotide pools in hydroxyurea-resistant mutants.
Ribonucleotide reductase activity and deoxyribonucleoside triphosphate (dNTP) pools were examined in several Syrian hamster melanoma cell mutants which are resistant to hydroxyurea (HU), an inhibitor of ribonucleotide reductase, and which also show increased resistance to bromdeoxyuridine (BrdU) mutagenesis. For most of the mutants, resistance to HU and BrdU mutagenesis is associated with increased levels of ribonucleotide reductase activity. No evidence was found for qualitative alterations in the ribonucleotide reductase in the mutant cells. The dNTP pools in the mutants are somewhat resistant to the perturbations can be produced in wild-type cells by the addition of BrdU, although significant perturbations can be produced in the mutants by higher concentrations of BrdU. The decrease in BrdU-induced nucleotide pool perturbations may account for the resistance of the mutants to BrdU mutagenesis.
D000818:Animals; D001973:Bromodeoxyuridine / Q000494:pharmacology*; D002453:Cell Cycle / Q000187:drug effects; D002460:Cell Line; D002467:Cell Nucleus / Q000187:drug effects / Q000502:physiology; D006224:Cricetinae; D003854:Deoxyribonucleotides / Q000378:metabolism*; D004351:Drug Resistance; D006918:Hydroxyurea / Q000494:pharmacology*; D007700:Kinetics; D008545:Melanoma; D008647:Mesocricetus; D009154:Mutation; D012264:Ribonucleotide Reductases / Q000235:genetics / Q000378:metabolism*
D003854:Deoxyribonucleotides; D012264:Ribonucleotide Reductases; D001973:Bromodeoxyuridine; D006918:Hydroxyurea