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.

journal_name

Ind Health

journal_title

Industrial health

authors

Takagi A,Yamada T,Hayashi K,Nakade Y,Kojima T,Takamatsu J,Shibata E,Ichihara G,Takeuchi Y,Murate T

doi

10.2486/indhealth.40.371

keywords:

subject

Has Abstract

pub_date

2002-10-01 00:00:00

pages

371-4

issue

4

eissn

0019-8366

issn

1880-8026

journal_volume

40

pub_type

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