Linked Life Data

6480447

Source:http://linkedlifedata.com/resource/pubmed/id/6480447

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
9
pubmed:dateCreated
1984-11-16
pubmed:abstractText
It is well known that endogenous sulfhydryls are radioprotective in mammalian cells. Their comparable role in chemotherapeutic drug toxicity has been known for almost as long but less well defined. Thiol depletion as a mechanism responsible for enhanced cytotoxicity of melphalan was assayed by pretreatment of cells in vitro with misonidazole and buthionine sulfoximine (BSO). Hypoxic cell sensitizers, such as MISO, deplete endogenous thiols by metabolic activation under hypoxic conditions to thiol reactive intermediates, whereas BSO specifically inhibits a key enzyme in the synthesis of glutathione. For a given level of thiol reduction, sensitization to melphalan was far greater by preincubation with MISO than it was for BSO. This indicated that thiol reduction itself was not the sole factor involved in chemosensitization by MISO. As evidence that the method of thiol depletion predisposes to the expression of biological damage, it was shown that cells preincubated with MISO were appreciably more vulnerable to oxidative stress than those exposed to BSO. BSO was shown to totally inhibit the repair of damage from a preincubation treatment with MISO, demonstrating that recovery is dependent upon thiol regeneration. Thiol depletion "per se" is a good qualitative but not necessarily a quantitative indicator of chemosensitization--the biological and biochemical function of the thiol depleting agents used influences further drug interactions. The results of the study with these two agents suggest that thiols may play a potentially more critical role in the repair rather than the initiation of drug-induced damage.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
0360-3016
pubmed:author
pubmed:issnType
Print
pubmed:volume
10
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1599-602
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
1984
pubmed:articleTitle
Chemosensitization: do thiols matter?
pubmed:publicationType
Journal Article, Comparative Study, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't