title: Arsenic trioxide promotes mitochondrial DNA mutation and cell apoptosis in primary APL cells and NB4 cell line.
abstract: This study aimed to investigate the effects of arsenic trioxide (As(2)O(3)) on the mitochondrial DNA (mtDNA) of acute promyelocytic leukemia (APL) cells. The NB4 cell line was treated with 2.0 micromol/L As(2)O(3) in vitro, and the primary APL cells were treated with 2.0 micromol/L As(2)O(3) in vitro and 0.16 mg kg(-1) d(-1) As(2)O(3) in vivo. The mitochondrial DNA of all the cells above was amplified by PCR, directly sequenced and analyzed by Sequence Navigatore and Factura software. The apoptosis rates were assayed by flow cytometry. Mitochondrial DNA mutation in the D-loop region was found in NB4 and APL cells before As(2)O(3) use, but the mutation spots were remarkably increased after As(2)O(3) treatment, which was positively correlated to the rates of cellular apoptosis, the correlation coefficient: r (NB4-As2O3)=0.973818, and r (APL-As2O3)=0.934703. The mutation types include transition, transversion, codon insertion or deletion, and the mutation spots in all samples were not constant and regular. It is revealed that As(2)O(3) aggravates mtDNA mutation in the D-loop region of acute promyelocytic leukemia cells both in vitro and in vivo. Mitochondrial DNA might be one of the targets of As(2)O(3) in APL treatment.
authors.affiliation: Division of Neurology, the Ninth Clinical Medical College of Beijing University (Shijitan Hospital), Beijing, 100038, China. victor65@126.com.
authors.forename: Ran
authors.initials: R
authors.lastname: Meng
authors.affiliation: The First Hospital of Harbin Medical University, Harbin, 150001, China. Jinzhouh85@163.com.
authors.forename: Jin
authors.initials: J
authors.lastname: Zhou
authors.affiliation: Management Information System, University of International Business and Economics, Beijing, 100029, China.
authors.forename: Meng
authors.initials: M
authors.lastname: Sui
authors.affiliation: Department of Radiology, Cambridge University Hospitals NHS Foundation Trust Box 219 Level 5, Addenbrooke's Hospital, Cambridge, CB2 0QQ, UK.
authors.forename: ZhiYong
authors.initials: Z
authors.lastname: Li
authors.affiliation: Division of Neurology, the Ninth Clinical Medical College of Beijing University (Shijitan Hospital), Beijing, 100038, China.
authors.forename: GuoSheng
authors.initials: G
authors.lastname: Feng
authors.affiliation: The First Hospital of Harbin Medical University, Harbin, 150001, China.
authors.forename: BaoFeng
authors.initials: B
authors.lastname: Yang
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D000077237:Arsenic Trioxide; D001152:Arsenicals / Q000494:pharmacology*; D001483:Base Sequence; D045744:Cell Line, Tumor; D004252:DNA Mutational Analysis; D004272:DNA, Mitochondrial / Q000235:genetics*; D006801:Humans; D015473:Leukemia, Promyelocytic, Acute / Q000235:genetics / Q000473:pathology; D008969:Molecular Sequence Data; D009154:Mutation / Q000187:drug effects*; D010087:Oxides / Q000494:pharmacology*; D016133:Polymerase Chain Reaction; D014407:Tumor Cells, Cultured
chemical_list: D000970:Antineoplastic Agents; D001152:Arsenicals; D004272:DNA, Mitochondrial; D010087:Oxides; D000077237:Arsenic Trioxide