title: Molecular analysis of Tripterygium hypoglaucum (level) Hutch-induced mutations at the HPRT locus in human promyelocytic leukemia cells by multiplex polymerase chain reaction.
abstract: The genotoxicity and cytotoxicity of a Chinese medicinal herb, Tripterygium hypoglaucum (level) Hutch (THH), was investigated in human promyelocytic leukemia (HL-60) cells using the hypoxanthine-guanine phosphoribosyltransferase mutation assay. THH showed clear cytotoxicity and mutagenicity in HL-60 cells at concentrations between 6.7 and 20.0 mg/ml. When the mutants were characterized by techniques based on multiplex PCR, 46.6% of induced mutants were found to have deletions, whereas only 7.7% of spontaneous mutants showed deletions. The rest were not characterized, but were assumed to be mainly point mutations. Mapping of all intragenic deletion breakpoints showed a random distribution of breakpoints in nine exons. Deletion of exon 1 appeared as the only whole gene deletion, while deletions of exon 7/8 and 9 often occurred concomitantly (71.4%). It is concluded that THH is mutagenic in HL-60 cells, predominantly inducing deletions. Since this herb is widely used as a traditional medicine, its genotoxicity should be assessed in vivo in treated humans.
authors.affiliation: Department of Hygiene Toxicology, College of Preventive Medicine, Third Military Medical University, Chongqing 400038, People's Republic of China.
authors.forename: Sheng Xue
authors.initials: SX
authors.lastname: Liu
authors.forename: Jia
authors.initials: J
authors.lastname: Cao
authors.forename: Hui
authors.initials: H
authors.lastname: An
mesh_terms: D004273:DNA, Neoplasm / Q000187:drug effects / Q000235:genetics; D004305:Dose-Response Relationship, Drug; D005091:Exons / Q000235:genetics; D018922:HL-60 Cells / Q000737:chemistry / Q000187:drug effects*; D006801:Humans; D007041:Hypoxanthine Phosphoribosyltransferase / Q000235:genetics*; D015473:Leukemia, Promyelocytic, Acute / Q000473:pathology*; D016296:Mutagenesis; D009152:Mutagenicity Tests; D010936:Plant Extracts / Q000633:toxicity*; D018517:Plant Roots / Q000737:chemistry; D017354:Point Mutation; D016133:Polymerase Chain Reaction / Q000379:methods*; D017384:Sequence Deletion; D029757:Tripterygium / Q000737:chemistry*
chemical_list: D004273:DNA, Neoplasm; D010936:Plant Extracts; D007041:Hypoxanthine Phosphoribosyltransferase