title: Inhibition of myeloperoxidase activity have impact on the formation of DNA double-strand breaks induced by etoposide in HL-60 cell line.
abstract: Many studies have shown the role of myeloperoxidase (MPO) in leukemogenic activity of etoposide. The aim of our study was to determine whether inhibition of MPO activity has influence on the formation of double-stranded DNA breaks (DSBs) that may contribute to the characteristic of leukemia translocations. Studies were carried out on HL-60 cell line, which were preincubated with the MPO inhibitor 4-aminobenzoic acid hydrazide (ABAH), or antioxidant N-acetyl-L-cysteine (NAC), followed by incubation at different concentrations of etoposide (1-10 mM) for 4 hours. Cytotoxicity was investigated using propidium iodide staining. Marker of DSBs, a phosphorylated form of histone 2AX (gH2AX) was detected using immunocytochemical methods. Cells were analyzed by flow cytometry. ABAH significantly reduced the cytotoxicity and the gH2AX level induced by lower concentrations of etoposide (1 and 1.5 mM) and did not modify the action of higher concentration (10 mM) of this cytostatic drug. NAC exerted similar impact as ABAH on the level of gH2AX induced by etoposide. The results of this study suggest that MPO contributes to increase of the DSBs level induced by low concentrations of etoposide in myeloid cells.
authors.affiliation: Department of Cytobiology, Pharmaceutical Faculty, Jagiellonian University Medical College, Krakow, Poland. monika.papiez@uj.edu.pl.
authors.forename: Monika A
authors.initials: MA
authors.lastname: Papież
authors.forename: Wirginia
authors.initials: W
authors.lastname: Krzyściak
authors.forename: Magdalena
authors.initials: M
authors.lastname: Wąsik
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D053903:DNA Breaks, Double-Stranded / Q000187:drug effects*; D004249:DNA Damage / Q000187:drug effects; D005047:Etoposide / Q000494:pharmacology*; D005434:Flow Cytometry; D018922:HL-60 Cells; D006801:Humans; D059005:Topoisomerase II Inhibitors / Q000494:pharmacology*
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D059005:Topoisomerase II Inhibitors; D005047:Etoposide
keywords: 4-aminobenzoic acid hydrazide; double-stranded DNA breaks; etoposide; myeloperoxidase; γgH2AX