Linked Life Data

10806370

Source:http://linkedlifedata.com/resource/pubmed/id/10806370

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2000-7-6
pubmed:abstractText
The water disinfectant by-product dichloroacetonitrile (DCAN) is a direct-acting mutagen and induces DNA strand breaks in cultured human lymphoblastic cells. Cellular activation by environmental agents may exert detrimental effects to the cells. Activated macrophages produce reactive oxygen intermediates such as H(2)O(2), (-)OH and O(2). Therefore, the effect of various concentrations of DCAN (100-400 microM) on the activity macrophage cells (RAW 264.7) was studied. In these cells, DCAN-induced oxidative stress was characterized by the production of reactive oxygen intermediates (ROI). Also, the ratios of intracellular GSH/GSSG was assessed and used as a biomarker for oxidative stress. The secretion of TNF-alpha was assessed since macrophages are known to secrete TNF-alpha as a result of cellular oxidative stress. Electrophoretic detection of DNA degradation and light microscopy was utilized for the characterization of DCAN-induced apoptosis. Lactate dehydrogenase (LDH) leakage and trypan blue exclusion were used as markers of cellular necrosis. Following exposure to DCAN (200 microM and 400 microM), intracellular GSSG was increased (2.5-fold of control, P<0. 05). DCAN activation of RAW cells was detected by elevated levels of intracellular ROI (1.9-2.5-fold than control, P<0.05) and increased secretion of TNF-alpha (4.5 fold-than control, P <0.05). Elecrophoresis of genomic DNA of treated cells indicated a dose-dependent increase in degradation of genomic DNA. Morphological studies also indicated that exposure of RAW cells to 100 microM or 200 microM DCAN incites apoptotic cell death. At higher concentrations (400 microM), however, significant (P<0.05) increase in LDH leakage and decrease in cell viability (55% of control) indicative of cellular necrosis, were observed. These studies indicate that DCAN induces dose-dependent apoptosis or necrosis in RAW cells that could be due to the disturbance in intracellular redox status and initiation of ROI-mediated oxidative mechanisms of cellular damage.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
0887-2333
pubmed:author
pubmed:issnType
Print
pubmed:volume
14
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
199-210
pubmed:dateRevised
2009-4-10
pubmed:meshHeading
pubmed:year
2000
pubmed:articleTitle
Induction of oxidative stress and TNF-alpha secretion by dichloroacetonitrile, a water disinfectant by-product, as possible mediators of apoptosis or necrosis in a murine macrophage cell line (RAW).
pubmed:affiliation
Molecular Toxicology Laboratory, Department of Pathology, University of Texas Medical Branch, Galveston, TX 77555, USA. aahmed@utmb.edu
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, U.S. Gov't, Non-P.H.S.