SPECTRUM OF SPONTANEOUSLY OCCURRING MUTATIONS IN THE HPRT GENE OF THECHINESE-HAMSTER V79 CELL MUTANT V-H4, WHICH IS HOMOLOGOUS TO FANCONI-ANEMIA GROUP-A

The mitomycin C (MMC)-hypersensitive Chinese hamster V79 cell mutant V -H4 has a cellular phenotype similar to Fanconi anemia (FA), and has b een shown to be homologous to FA group A, To examine consequences of t he defect in V-H4 cells on spontaneous mutagenesis, we studied the fre quency and nature of spontaneous mutations at the hypoxanthine phospho ribosyltransferase (HPRT) locus in this mutant and the parental V79 ce lls, The mutation rates expressed as the number of mutations per cell per generation were 8.7 x 10(-7) and 3.7 x 10(-7) for V-H4 and V79 cel ls respectively. The molecular spectrum of 42 spontaneous hprt mutants of V-H4 cells was determined and compared with the previously describ ed spectrum of spontaneous mutations at the HPRT locus of Chinese hams ter V79 cells, The spectra of spontaneous mutations in the hprt gene o f both cell lines are predominated by base pair substitutions and spli ce mutations. Among the base changes, V-H4 shows a larger frequency of transitions (13/42; 31%) than transversions (3/42; 7%), whereas in V7 9 transversions are observed more often than transitions (P < 0.001; W ilcoxon test), The frequency of splice mutations in V-H4 (17/42; 40%), which affects exon 4 almost exclusively, is not significantly differe nt from V79. The fraction of deletions in V-H4 is low (6/42; 14%), and comparable to the level in V79. This is in contrast with the publishe d molecular spectrum of spontaneous hprt mutants in FA (group D) cells , which consists predominantly of deletions.