Phenotypic lag and mutation to 6-thioguanine resistance in diploid human lymphoblasts.
Mutants of a diploid human lymphoblast line resistant to 6-thioguanine (6TG) appear 6--16 generations after treatment with any of a diverse group of mutagents: methylnitrosourea (MNU), methylnitrosoguanidine (MNNG), ICR-191, 5-bromodeoxyuridine (BUdR). A hypothesis is advanced that expression of the 6-thioguanine-resistant state may require the removal of essentially all pre-existing hypoxanthine--guanine phosphoribosyl transferase (HGPRT) molecules via division, dilution, and protein turnover. Design of protocols for quantitative mutation assays requires attention to this phenomenon.
D001973:Bromodeoxyuridine / Q000494:pharmacology; D002478:Cells, Cultured; D003584:Cytological Techniques; D004351:Drug Resistance; D006801:Humans; D008213:Lymphocyte Activation; D008214:Lymphocytes; D008769:Methylnitronitrosoguanidine / Q000494:pharmacology; D008770:Methylnitrosourea / Q000494:pharmacology; D009154:Mutation; D009588:Nitrogen Mustard Compounds / Q000494:pharmacology; D010641:Phenotype; D013866:Thioguanine / Q000494:pharmacology*; D013997:Time Factors
D009588:Nitrogen Mustard Compounds; D008769:Methylnitronitrosoguanidine; D008770:Methylnitrosourea; D013866:Thioguanine; D001973:Bromodeoxyuridine