title: Spectrum of spontaneously occurring mutations in the HPRT gene of the Chinese hamster V79 cell mutant V-H4, which is homologous to Fanconi anemia group A.
abstract: The mitomycin C (MMC)-hypersensitive Chinese hamster V79 cell mutant V-H4 has a cellular phenotype similar to Fanconi anemia (FA), and has been shown to be homologous to FA group A. To examine consequences of the defect in V-H4 cells on spontaneous mutagenesis, we studied the frequency and nature of spontaneous mutations at the hypoxanthine phosphoribosyltransferase (HPRT) locus in this mutant and the parental V79 cells. 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 cells respectively. The molecular spectrum of 42 spontaneous hprt mutants of V-H4 cells was determined and compared with the previously described spectrum of spontaneous mutations at the HPRT locus of Chinese hamster V79 cells. The spectra of spontaneous mutations in the hprt gene of both cell lines are predominated by base pair substitutions and splice mutations. Among the base changes, V-H4 shows a larger frequency of transitions (13/42; 31%) than transversions (3/42; 7%), whereas in V79 transversions are observed more often than transitions (P < 0.001; Wilcoxon test). The frequency of splice mutations in V-H4 (17/42; 40%), which affects exon 4 almost exclusively, is not significantly different 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 published molecular spectrum of spontaneous hprt mutants in FA (group D) cells, which consists predominantly of deletions.
authors.affiliation: MGC-Department of Radiation Genetics and Chemical Mutagenesis, Leiden University, The Netherlands.
authors.forename: P
authors.initials: P
authors.lastname: Telleman
authors.forename: W J
authors.initials: WJ
authors.lastname: Overkamp
authors.forename: M Z
authors.initials: MZ
authors.lastname: Zdzienicka
mesh_terms: D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D006224:Cricetinae; D003412:Cricetulus; D004247:DNA; D004252:DNA Mutational Analysis; D005199:Fanconi Anemia / Q000235:genetics*; D007041:Hypoxanthine Phosphoribosyltransferase / Q000235:genetics*; D008969:Molecular Sequence Data; D009154:Mutation; D016133:Polymerase Chain Reaction; D012326:RNA Splicing / Q000235:genetics
chemical_list: D004247:DNA; D007041:Hypoxanthine Phosphoribosyltransferase