Concentration-dependent mutation of diploid human lymphoblasts by methylnitronitrosoguanidine: the importance of phenotypic lag.

The mutation of diploid human lymphoblasts by methylnitronitrosoguanidine (MNNG) was measured over the range of 0--45 ng of MNNG/ml of of medium. We found a 12-day lag in the phenotypic expression of 6-thioguanine resistance; the occurrence of this lag was independent of MNNG concentration. We hypothesize that the unexpectedly long lag period reflects a requirement for the loss of previously existing molecules of the enzyme hypoxanthine-guanine phosphoribosyltransferase (HGPRT) after mutation at the HGPRT locus.