Mutation of human lymphoblasts by methylnitrosourea.
The lag in phenotype expression of methylnitrosourea(MNU)-induced mutation to 6-thioguanine (6TG) resistance has been studied in a diploid human lymphoblastoid cell line. We find that a considerable period (8-12 days) elapses before new mutants appear in treated cultures; after 2 weeks, however, a stable maximum fraction is attained, as would be expected for a genetic mutation. We present preliminary data linking this phenotypic lag to the slow degradation rate of hypoxanthine-guanine phosphoribosyl transferase (HGPRT) and to an apparent requirement for very low (less than 0.2% normal) cellular HGPRT content in order for cells to be resistant to 10 mug 6TG/ml. A series of reconstruction experiments are presented, the results of which support the conclusion that selective pressures in the assay procedure do not bias the quantitative estimates of induced mutant fraction.
D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D002999:Clone Cells; D004171:Diploidy; D006801:Humans; D007041:Hypoxanthine Phosphoribosyltransferase / Q000378:metabolism; D008214:Lymphocytes / Q000187:drug effects / Q000378:metabolism*; D008770:Methylnitrosourea / Q000494:pharmacology*; D009154:Mutation; D009607:Nitrosourea Compounds / Q000494:pharmacology*; D010641:Phenotype; D013997:Time Factors
D009607:Nitrosourea Compounds; D008770:Methylnitrosourea; D007041:Hypoxanthine Phosphoribosyltransferase