Isolation of mutants of CHO cells resistant to 6 (p-hydroxyphenylazo)-uracil II. Mutants auxotrophic for deoxypyrimidines.
Two classes of CHO mutants resistant to the drug 6(p-hydroxyphenylazo)-uracil have been characterized. Both classes exhibited a nutritional requirement that could be satisfied by deoxypyrimidines and uridine but not other ribopyrimidines. A biochemical investigation of these mutants revealed a structural defect in ribonucleotide reductase resulting in a two- to fourfold increase in the Km for UDP and CDP. As a consequence of this lesion, the cells had imbalanced deoxypyrimidine pools and showed an increase in the rate of spontaneous mutation to 6-thioguanine resistance but not emetine resistance.
D000818:Animals; D002453:Cell Cycle / Q000187:drug effects; D002460:Cell Line; D006224:Cricetinae; D003412:Cricetulus; D003853:Deoxyribonucleosides / Q000378:metabolism*; D004351:Drug Resistance; D005260:Female; D006906:Hydroxyphenylazouracil / Q000494:pharmacology*; D007700:Kinetics; D009154:Mutation; D010053:Ovary; D012265:Ribonucleotides / Q000378:metabolism; D014498:Uracil / Q000031:analogs & derivatives*
D003853:Deoxyribonucleosides; D012265:Ribonucleotides; D006906:Hydroxyphenylazouracil; D014498:Uracil