Linked Life Data

2604748

Source:http://linkedlifedata.com/resource/pubmed/id/2604748

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
24
pubmed:dateCreated
1990-2-8
pubmed:abstractText
Metabolic activation is a prerequisite for the antitumor activity of certain drugs such as cyclophosphamide. In vitro assays require systems for metabolic activation to reveal the toxicity of such compounds for tumor cells. Although a number of methods utilizing systems for the in vitro metabolic activation of drugs have been published, practical assays applicable to large scale screening for such agents have been lacking. We, therefore, now report that incorporation of a liver subcellular fraction (S9) into a recently established cell growth inhibition assay (microculture tetrazolium assay) significantly increased the cytotoxicity of cyclophosphamide. Under optimal conditions, the 50% growth inhibitory concentration was decreased in the presence of S9 from more than 600 micrograms/ml to less than 4 micrograms/ml, depending upon the cell line. The method also proved suitable for studies investigating metabolic detoxification (enzymatically or non-enzymatically) by conjugation reactions. For example, glutathione (5 mM) markedly reduced the cytotoxicity of activated cyclophosphamide. In contrast, the addition of UDP glucuronate (10 mM) in the presence of the UDP-glucuronosyltransferase activator UDP-N-acetylglucosamine (10 mM) had little effect on cyclophosphamide toxicity.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
0006-2952
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
38
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
4477-83
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
1989
pubmed:articleTitle
A rapid in vitro method for the evaluation of potential antitumor drugs requiring metabolic activation by hepatic S9 enzymes.
pubmed:affiliation
Dr Karl Thomae Gmbh, Biberach, West Germany.
pubmed:publicationType
Journal Article, Comparative Study