8-Azaguanine resistance in mammalian cells. I. Hypoxanthine-guanine phosphoribosyltransferase.
Chinese hamster cells were treated with ethyl methanesulfonate or N-methyl-N'-nitro-N-nitrosoguanidine, and mutants resistant to 8-azaguanine were selected and characterized. Hypoxanthine-guanine phosphoribosyltransferase activity of sixteen mutants is extremely negative, making them suitable for reversion to HGPRTase(+). Ten of the extremely negative mutants revert at a frequency higher than 10(-7) suggesting their point mutational character. The remaining mutants have demonstrable HGPRTase activity and are not useful for reversion analysis. Five of these mutants have < 2% HGPRTase and are presumably also HGPRTase point mutants. The remaining 14 mutants utilize exogenous hypoxanthine for nucleic acid synthesis poorly, and possess 20-150% of wild-type HGPRTase activity in in vitro. Their mechanism of 8-azaguanine resistance is not yet defined.
D000225:Adenine / Q000378:metabolism; D000473:Alkanes / Q000494:pharmacology; D000818:Animals; D001375:Azaguanine / Q000494:pharmacology*; D002247:Carbon Isotopes; D002999:Clone Cells; D006224:Cricetinae; D004247:DNA / Q000096:biosynthesis; D004351:Drug Resistance; D007042:Hypoxanthines / Q000378:metabolism; D008168:Lung / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D009154:Mutation; D009604:Nitrosoguanidines / Q000494:pharmacology; D010428:Pentosephosphates; D010430:Pentosyltransferases; D010756:Phosphoric Acids; D012313:RNA / Q000096:biosynthesis; D012266:Ribose; D012641:Selection, Genetic; D013451:Sulfonic Acids / Q000494:pharmacology; D014316:Tritium
D000473:Alkanes; D002247:Carbon Isotopes; D007042:Hypoxanthines; D009604:Nitrosoguanidines; D010428:Pentosephosphates; D010756:Phosphoric Acids; D013451:Sulfonic Acids; D014316:Tritium; D012313:RNA; D012266:Ribose; D004247:DNA; D010430:Pentosyltransferases; D000225:Adenine; D001375:Azaguanine