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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2-3
pubmed:dateCreated
2005-4-20
pubmed:abstractText
It is well known that formaldehyde (HCHO) and reactive oxygen species (ROS), such as free radicals, are cytotoxic as well as potentially carcinogenic. Although the individual effects of these reactants on cells have been investigated, the cytotoxicity exerted by the coexistence of HCHO and reactive radicals is poorly understood. The present study using Jurkat cells demonstrated that the coexistence of HCHO with water-soluble radical initiator, 2,2'-azobis-[2-(2-imidazolin-2-yl)propane] dihydrochloride (AIPH) dramatically decreased cell viability, and that under such conditions scant cell death was observable induced by either of the reactants alone. Based on the results of phosphatidylserine exposure and caspase activation, this observed cell death, in fact, was apparently necrotic rather than apoptotic. To understand the mechanisms of the cell toxicity of HCHO and AIPH, we assessed two kinds of oxidative stress markers such as cellular glutathione (GSH) content and cellular ROS, and the DNA-protein cross-links, which formed as the result of HCHO treatment. A marked decrease in total cellular GSH was observed not only in the case of the coexistence conditions but also with AIPH alone. Dichlorodihydrofluorescein (DCF) assay revealed that cellular ROS were synergistically increased before cell death. The formation of DNA-protein cross-links was observed in the presence of HCHO and AIPH, and the extent was similar to HCHO alone. Co-incubation with semicarbazide, which inactivates HCHO, prevented this cell death induced by a combination of HCHO and AIPH. Semicarbazide also exhibited an inhibitory effect on the synergistic increment of cellular ROS and the formation of DNA-protein cross-links. These results suggest that the free radicals from AIPH induced GSH reduction, while HCHO resulted in the formation of DNA-protein cross-links, eventuating in a synergistic, incremental increase of cellular ROS and cell death brought about by this combination.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
0300-483X
pubmed:author
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
210
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
235-45
pubmed:meshHeading
pubmed:year
2005
pubmed:articleTitle
Cytotoxic effect of formaldehyde with free radicals via increment of cellular reactive oxygen species.
pubmed:affiliation
Human Stress Signal Research Center (HSSRC), National Institute of Advanced Industrial Science and Technology (AIST), 1-8-31 Midorigaoka, Ikeda, Osaka 563-8577, Japan. yoshiro-saito@aist.go.jp
pubmed:publicationType
Journal Article