Linked Life Data

9205076

Source:http://linkedlifedata.com/resource/pubmed/id/9205076

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
13
pubmed:dateCreated
1997-7-25
pubmed:abstractText
The initial metabolism of ifosfamide (IFO) consists of two different pathways, which lead to the alkylating metabolite 4-hydroxy-IFO and to chloroacetaldehyde (CAA). CAA has been reported to cause side effects, such as neuro- and nephrotoxicity, whereas no direct antitumor effect has been described thus far. Therefore, two human tumor cell lines (MXI and S117) and a renal tubular cell line (Landa Leiden) were exposed to 4-hydroxy-IFO, CAA, and a combination of both. The concentrations used were in the same range as measured in the blood of 10 patients treated with 5 g/m2 IFO. The cell survival was measured using the MTT assay. Similar dose-response curves were found for both metabolites. For the MX1 tumor, the IC50s of 4-hydroxy-IFO and CAA were 10.8 and 8.6 microM, respectively. For the reduction of S117 cell survival, higher concentrations of the metabolites were needed (25.0 microM 4-hydroxy-IFO and 15.3 microM CAA). Combination treatment of the cells resulted in an approximately additive effect. Both metabolites exhibited similar toxicity against Landa Leiden cells. Our results indicate that CAA has its own cytotoxic profile against tumor cells. Hence, we conclude that the molecular mechanism of action of IFO seems to be only in part an alkylating effect and that CAA may play an important role in the therapeutic efficacy of IFO.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
0008-5472
pubmed:author
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
57
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2676-80
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
1997
pubmed:articleTitle
Ifosfamide cytotoxicity on human tumor and renal cells: role of chloroacetaldehyde in comparison to 4-hydroxyifosfamide.
pubmed:affiliation
Department of Internal Medicine, Medical University of Lübeck, Germany.
pubmed:publicationType
Journal Article, Comparative Study