Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
9
pubmed:dateCreated
1990-5-31
pubmed:abstractText
The polyamine biosynthesis inhibitor alpha-difluoromethylornithine (DFMO) has been shown to potentiate the cytotoxicity of 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) in 9L rat brain tumor cells and in non-central nervous system human cancer cells in vitro, but the effects on a human brain tumor cell line have not been reported. Because BCNU is one of the main chemotherapeutic agents used clinically for the treatment of brain tumors, the effect of DFMO treatment on cell growth and potentiation of cytotoxicity was studied in vitro in U-251 MG and SF-126 cells, human tumor cell lines derived from malignant glioma tissue. Pretreatment of U-251 MG with 1 mM DFMO depleted cells of putrescine and spermidine within 48 h but did not sensitize cells to BCNU treatment even after a pretreatment of 72 h. DFMO treatment had no effect on the number of interstrand cross-links formed in BCNU-treated cells. Even treatment with 5 mM DFMO for 72 h caused only the suggestion of potentiation of BCNU cell kill. In contrast, a 72-h pretreatment with 1 mM DFMO decreased the cytotoxic effect of cis-diammine-dichloroplatinum(II) and caused a 38% decrease in the number of DNA interstrand cross-links formed. The glutathione content and cell cycle distribution of U-251 MG cells were not affected by DFMO pretreatment. Because Phase II clinical trials with DFMO and BCNU have shown promise for the treatment of anaplastic astrocytomas in humans, a second brain tumor cell line, SF-126, was studied. In this cell line a consistent potentiation of BCNU cytotoxicity (dose enhancement of 1.2 at the 10% survival level) was observed in cells pretreated with 1 mM DFMO for 72 h.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
0008-5472
pubmed:author
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
50
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2769-72
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
1990
pubmed:articleTitle
Effect of alpha-difluoromethylornithine on 1,3-bis(2-chloroethyl)-1-nitrosourea and cis-diamminedichloroplatinum(II) cytotoxicity, DNA interstrand cross-linking, and growth in human brain tumor cell lines in vitro.
pubmed:affiliation
Department of Neurological Surgery, School of Medicine, University of California, San Francisco 94143.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't