Mutations causing deficiency of APRT in fibroblasts cultured from human heterozygous for mutant APRT alleles

Frequent mutation to adenine analog resistance in diploid human cells reflected heterozygosity for recessive alleles affecting expression of the adenine phosphoribosyltransferase (APRT) locus. Cells from both parents of APRT-deficient sibs were heterozygous and had rates of spontaneous mutation to 2,6-diaminopurine (DAP) resistance of 6.0 x 10(-5) and 16 x 10(-5) per cell generation. Spontaneous DAP-resistant mutants were not observed in cultures of homozygous cells. Almost all mutants of proven heterozygous cultures were APRT deficient and could not use adenine for growth. Frequent DAP-resistant mutations identified heterozygous strain 438, which carried an allele encoding a partially defective form of APRT. All DAP-resistant mutants of strain 438 were partially APRT deficient and could use adenine for growth. The frequency of MNNG-induced DAP-resistant mutants in homozygous strains was approximately the square of the induced frequency in heterozygous strains.