title: Derepression of HPRT locus on inactive X chromosome of human lymphoblastoid cell line.
abstract: Human XX lymphoblastoid cells with a deletion in the HPRT locus on the active X were exposed to HPRT clone pHPT32. HPRT+ isolates GPT3 and GPT5 lacked pHPT32 DNA, suggesting that their HPRT+ phenotype resulted from expression of a cellular gene. GPT3 mutated to thioguanine resistance at least 100 times more frequently than cells in which the expressed HPRT locus was on the active X. Most GPT3-derived HPRT- had lost one entire X chromosome, indicating that the HPRT+ phenotype of GPT3 resulted from derepression of the HPRT locus on its inactive X. Virtually unchanged G6PD and PGK activities and the presence of a late-replicating X in GPT3 suggest that derepression of the inactive X was not general. Eleven of the GPT3-derived mutants had a tiny centric remnant that may result from a frequently operative mechanism of X chromosome loss. The detection of partial or complete loss of an X by direct selection presents unusual opportunities for genotoxicity detection with human cells.
authors.forename: N
authors.initials: N
authors.lastname: Nadon
authors.forename: G
authors.initials: G
authors.lastname: Sekhon
authors.forename: L J
authors.initials: LJ
authors.lastname: Brown
authors.forename: N
authors.initials: N
authors.lastname: Korn
authors.forename: J W
authors.initials: JW
authors.lastname: Petersen
authors.forename: J
authors.initials: J
authors.lastname: Strandtmann
authors.forename: C
authors.initials: C
authors.lastname: Chang
authors.forename: R
authors.initials: R
authors.lastname: DeMars
mesh_terms: D002460:Cell Line; D002871:Chromosome Banding; D002872:Chromosome Deletion; D003001:Cloning, Molecular; D004794:Enzyme Repression; D005796:Genes; D006801:Humans; D007041:Hypoxanthine Phosphoribosyltransferase / Q000096:biosynthesis / Q000235:genetics*; D007621:Karyotyping; D007945:Leukemia, Lymphoid; D009154:Mutation; D009693:Nucleic Acid Hybridization; D014960:X Chromosome
chemical_list: D007041:Hypoxanthine Phosphoribosyltransferase