title: Involvement of caspase 3 mediated apoptosis in hematopoietic cytotoxicity of metabolites of ethylene glycol monomethyl ether.
abstract: The hematopoietic toxicity of ethylene glycol monomethyl ether (EGME) and its metabolites, methoxy acetaldehyde (MALD) and methoxyacetic acid (MAA), was analyzed using human bone marrow cells from a lymphoma patient without bone marrow involvement and a human leukemia cell line, HL60. After 24-hour incubation, the concentrations of 50 percent inhibition (IC50) of human hematopoietic progenitor cells with MALD or MAA were 3 mM and 3.9 mM, respectively, and EGME (10 mM or more) did not show any cytotoxicity. IC50 (after 48-hour exposure) of MALD and MAA on HL60 cells were 2.45 mM and 5.6 mM, respectively, suggesting that both hematopoietic progenitor cells and HL60 have a similar sensitivity. DNA ladder formation, a characteristics of apoptosis, was observed in MALD- or MAA-treated HL60 cells, but not in EGME-treated samples. Caspase-3 enzyme activity, the effector of the apoptotic process, was greatly enhanced with MALD treatment. The inhibitor of caspase-3 repressed cell death induced with MALD as well as MAA.
authors.affiliation: Department of Medical Technology, Nagoya University School of Health Sciences, Daiko Minami 1-1-20, Higashi-ku, Nagoya 461-8673, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Takagi
authors.forename: Takayuki
authors.initials: T
authors.lastname: Yamada
authors.forename: Koji
authors.initials: K
authors.lastname: Hayashi
authors.forename: Yuusuke
authors.initials: Y
authors.lastname: Nakade
authors.forename: Tetsuhito
authors.initials: T
authors.lastname: Kojima
authors.forename: Junki
authors.initials: J
authors.lastname: Takamatsu
authors.forename: Eiji
authors.initials: E
authors.lastname: Shibata
authors.forename: Gaku
authors.initials: G
authors.lastname: Ichihara
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Takeuchi
authors.forename: Takashi
authors.initials: T
authors.lastname: Murate
mesh_terms: D000079:Acetaldehyde / Q000633:toxicity* / Q000031:analogs & derivatives; D000085:Acetates / Q000633:toxicity*; D017209:Apoptosis / Q000502:physiology*; D053148:Caspase 3; D020169:Caspases / Q000502:physiology*; D005026:Ethylene Glycols / Q000378:metabolism / Q000633:toxicity*; D018922:HL-60 Cells; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000187:drug effects*; D006801:Humans; D066298:In Vitro Techniques; D007564:Japan; D008297:Male
chemical_list: D000085:Acetates; D005026:Ethylene Glycols; C049826:2-methoxyacetaldehyde; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases; C005219:methyl cellosolve; C013598:methoxyacetic acid; D000079:Acetaldehyde