Diploid azaguanine-resistant mutants of cultured human fibroblasts.

Two azaguanine-resistant clones of cultured, human fibroblasts were isolated from unrelated strains of karyotypically normal, male cells. The most resistant mutant has little hypoxanthine-guanine phosphoribosyltransferase activity, is virtually unable to incorporate hypoxanthine (a normal substrate of the enzyme), and resembles fibroblasts cultured from boys with the Lesch-Nyhan syndrome. The less resistant mutant has about one-third as much enzyme activity as its parent strain and is less able to utilize hypoxanthine. Both mutants are morphologically and karyotypically normal. These mutations may have occurred at the X-chromosomal, hypoxanthine-guanine phosphoribosyltransferase locus and may provide a realistic experimental model for studying mutation in human genetic material.