Linked Life Data

16980241

Source:http://linkedlifedata.com/resource/pubmed/id/16980241

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2006-9-18
pubmed:abstractText
Sulfur mustard (SM) is a powerful cytotoxic agent as well as a potent vesicant, mutagen, and carcinogen. This compound reacts with glutathione (GSH) and forms GSH-SM conjugates that appear to be excreted through the mercapturic acid pathway in mammals. The question of whether glutathione-S-transferases (GST) are involved in enzymatic formation of these conjugates remains unresolved. In previous studies, ethacrynic acid (EAA), a putative inhibitor of this transferase, and oltipraz, a known inducer,were ineffective in modulating this enzyme in cultured normal human epidermal keratinocytes (NHEK) so this hypothesis could not be tested. Higher levels of intracellular GSH appeared to be solely responsible for resistance of EAA-pretreated cells to SM. A better inducer of GST was needed to test whether this enzyme could be used to modify cytotoxicity following SM exposure. D,L-sulforaphane (DLS), a compound from broccoli extract known to be a potent inducer of this enzyme, was tested for GST induction in cultured NHEK. The enzyme levels increased optimally (40%) in these cells within 4 hours using 0.5 microg DLS/mL over a 48 hour incubation period. When the drug was removed by washing, and pretreated cells were challenged with 0-200 microM SM, there was a 10%-15% increase in survival at 24 hours compared with non-pretreated SM controls. This protective effect due to increased levels of GST was abolished at 300 microM sulfur mustard, where there was no difference in survival between pretreated and non-pretreated controls. Glutathione levels were also assessed and showed no increase at 4 hours in cultured NHEK with DLS pretreatment and appear not to be responsible for this protection against SM.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:issn
1556-9527
pubmed:author
pubmed:issnType
Print
pubmed:volume
25
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
155-63
pubmed:dateRevised
2009-11-17
pubmed:meshHeading
pubmed:year
2006
pubmed:articleTitle
Pretreatment of human epidermal keratinocytes with D,L-sulforaphane protects against sulfur mustard cytotoxicity.
pubmed:affiliation
U.S. Army Medical Research Institute of Chemical Defense, Aberdeen Proving Ground, Maryland, USA. clark.gross@us.army.mil
pubmed:publicationType
Journal Article