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: Akira Takagi, Takayuki Yamada, Koji Hayashi, Yuusuke Nakade, Tetsuhito Kojima, Junki Takamatsu, Eiji Shibata, Gaku Ichihara, Yasuhiro Takeuchi, Takashi Murate
• Journal: Industrial health (Ind Health) Vol. 40 Issue 4 Pg. 371-4 (Oct 2002) ISSN: 0019-8366 [Print] Japan
• PMID: 12502240 (Publication Type: Journal Article)

Chemical References

• Acetates
• Ethylene Glycols
• 2-methoxyacetaldehyde
• CASP3 protein, human
• Caspase 3
• Caspases
• methyl cellosolve
• methoxyacetic acid
• Acetaldehyde

Topics

• Acetaldehyde (toxicity)
• Acetates (toxicity)
• Apoptosis (physiology)
• Caspase 3
• Caspases (physiology)
• Ethylene Glycols (metabolism, toxicity)
• HL-60 Cells
• Hematopoietic Stem Cells (cytology, drug effects)
• Humans
• In Vitro Techniques
• Japan
• Male