Linked Life Data

1958233

Source:http://linkedlifedata.com/resource/pubmed/id/1958233

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
11
pubmed:dateCreated
1991-12-31
pubmed:abstractText
The cellular reduction of 2-nitroimidazoles under hypoxic conditions can lead to cell killing. One of the postulated toxic intermediates is the two-electron reduction product, the nitrosoimidazole. 1-Methyl-2-nitrosoimidazole (INO) was used as a model to study the reactivity of 2-nitrosoimidazoles with sulfhydryls. INO reacted within minutes with bovine serum albumin (BSA) in a stoichiometric fashion as measured by the loss of its characteristic absorption at 360 nm. It appeared to react specifically with the SH group of BSA as demonstrated by the loss of 5,5'-dithiobis-2- nitrobenzoic acid (DTNB) reactive groups and by the loss of INO reactivity if BSA was previously reacted with DTNB. INO also depleted glutathione (GSH) and protein sulfhydryls (Pr-SH) in Chinese hamster ovary (CHO) cells in a concentration-dependent fashion. INO at 25 microM, a non-toxic concentration in terms of cell colony-forming ability, depleted GSH to 10-20% of control levels within 5 min after treatment. Pr-SH were depleted more slowly to 60% of control levels. GSH recovered to near control levels over 3-4 hr but Pr-SH remained depressed. The recovery of GSH was blocked by buthionine sulfoximine (BSO), suggesting that the recovery was due to de novo synthesis of GSH. At a toxic concentration of INO (45 microM), GSH was again depleted to 10-20% and Pr-SH to 50% of control levels. No recovery of either was observed up to 4 hr. The effect of this extensive oxidative stress on intracellular calcium (Ca2+i) levels was monitored using 1-[2-amino-5-(6-carboxyindole-2-yl)-phenoxyl]-2- (2'-amino-5'-methylphenoxy)-ethane-N,N,N',N'-tetraacetic acid pentaacetoxy methylester (INDO-1 AM). At toxic concentrations of INO, Ca2+i increased in a sustained, non-physiological manner starting at approximately 60 min after the addition of INO. No increase in Ca2+i was observed when cells were treated with nontoxic concentrations of INO. INO toxicity may be modulated by an uncontrolled influx of Ca2+ which can trigger the activation of cellular enzymes and lead to cell death.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
0006-2952
pubmed:author
pubmed:issnType
Print
pubmed:day
6
pubmed:volume
42
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2153-61
pubmed:dateRevised
2005-11-17
pubmed:meshHeading
pubmed:year
1991
pubmed:articleTitle
Effect of 1-methyl-2-nitrosoimidazole on intracellular thiols and calcium levels in Chinese hamster ovary cells.
pubmed:affiliation
Experimental Therapeutics Division, Ontario Cancer Institute, Toronto, Canada.
pubmed:publicationType
Journal Article