title: Toxic effects of arsenic (As3+) and other metal ions on acute promyelocytic leukemia cells.
abstract: Since arsenic compounds reportedly induced complete remission in patients with acute promyelocytic leukemia (APL) in China, we studied the in vitro effect of metal ions including As3+, As5+, Cd2+, Ga3+, Ge4+, Hg2+, Se4+, and Zn2+ on myeloid cell lines. One-tenth microM As3+ caused growth suppression and morphological changes resembling differentiation in NB4 cells, but did not induce the maturation-markers, CD11b, CD14 and NBT-reductase. More than 1 microM As3+ caused the time- and dose-dependent apoptosis of NB4 cells. Other metal ions at the same concentrations induced neither morphological changes nor apoptosis in myeloid cell lines including NB4, whereas Cd2+, Ga3+, and Hg2+ induced moderate and non-specific growth suppression. All-trans retinoic acid (ATRA)-resistant NB4 cells were similarly sensitive to As3+. Among the clinical leukemia samples, As3+ was selectively toxic to APL cells regardless of ATRA-sensitivity. These findings suggest that APL cells are sensitive to As3+, and that As3+ acts on APL cells via a different pathway than ATRA.
authors.affiliation: Department of Medicine, Nagoya University Branch Hospital, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Kitamura
authors.forename: H
authors.initials: H
authors.lastname: Yoshida
authors.forename: R
authors.initials: R
authors.lastname: Ohno
authors.forename: T
authors.initials: T
authors.lastname: Naoe
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D001151:Arsenic / Q000627:therapeutic use / Q000633:toxicity*; D002455:Cell Division / Q000187:drug effects; D006801:Humans; D015473:Leukemia, Promyelocytic, Acute / Q000188:drug therapy* / Q000473:pathology; D011042:Poisons / Q000627:therapeutic use / Q000633:toxicity*; D014407:Tumor Cells, Cultured
chemical_list: D011042:Poisons; D001151:Arsenic