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.