Linked Life Data

7517170

Source:http://linkedlifedata.com/resource/pubmed/id/7517170

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
1994-8-1
pubmed:abstractText
Ifosfamide (IF) and cyclophosphamide (CP) are highly effective alkylating cytostatic drugs. IF and CP have to be activated through a metabolic step in vivo; numerous metabolites are known. While both IF and its structural isomer CP have severe urotoxic side effects, only IF is also a nephrotoxic drug, causing tubular damage resulting in Fanconi syndrome in some cases. Little information is available regarding the pathogenic mechanism of tubular damage by IF. We used the renal epithelial cell line LLC-PK1, which has many properties of the proximal tubule, in order to investigate the toxicity of IF and CP and of their reactive metabolites 4-hydroxy-IF (4-OH-IF), 4-hydroxy-CP (4-OH-CP), acrolein and chloroacetaldehyde (CAA). Protein content of monolayers, DNA and RNA synthesis were determined by standard techniques (thymidine and uridine incorporation). IF and CP had the lowest toxicities of all compounds tested. Both drugs inhibited thymidine incorporation by about 30% at a concentration of 300 mumol/l after 1 h incubation. 4-OH-IF and 4-OH-CP were significantly more toxic than the parent drugs. Thymidine incorporation, the most sensitive parameter, was reduced by about 70% by 300 mumol/l of either compound. In addition, 4-OH-CP reduced the total protein content of monolayers. 4-OH-IF did not effect protein content and RNA synthesis. Acrolein, the most toxic metabolite tested, reduced all three parameters significantly at concentrations of 50-75 mumol/l after 1 h.(ABSTRACT TRUNCATED AT 250 WORDS)
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
0931-041X
pubmed:author
pubmed:issnType
Print
pubmed:volume
8
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
157-63
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
1994
pubmed:articleTitle
Toxicity of ifosfamide, cyclophosphamide and their metabolites in renal tubular cells in culture.
pubmed:affiliation
Department of Paediatrics, Albert-Ludwigs-Universität Freiburg, Germany.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't