Linked Life Data

2400809

Source:http://linkedlifedata.com/resource/pubmed/id/2400809

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
1990-10-23
pubmed:abstractText
Preclinical studies of resistance to alkylating agents in the Lewis x Brown Norway hybrid (LBN) rat model of acute myeloid leukemia (AML) have hitherto been limited by the sensitivity of LBN AML cells to cyclophosphamide (CY). We developed a CY-resistant subline of LBN AML by serial intravenous (IV) passage of AML cells followed by in vivo exposure to CY (100 mg/kg) 14 days later. After 18 and subsequent passages, CY-treated AML cells remained viable despite ex vivo incubation with 70 to 100 mumol/L 4-hydroperoxycyclophosphamide (4HC) or in vivo exposure to 100 to 300 mg/kg of CY. Once established, resistance to incubation with 4HC was stable in LBN AML cells after at least six serial in vivo passages without exposure to CY. Nevertheless, both control and CY-treated AML cells demonstrated similar dose-dependent sensitivity to 100 to 500 mumol/L phosphoramide mustard (PhM), the active alkylating end-product of CY activation in vivo. Levels of aldehyde dehydrogenase (ALDH), which inactivates CY by prevention of formation of PhM, were significantly elevated in these CY-resistant AML cells: cytosolic and particulate ALDH fractions from these cells were 11 to 13 times control with NAD cofactor and propanal substrate and three to four times control with NADP cofactor and benzaldehyde substrate. Further studies with this animal model of AML, in which resistance to CY is mediated by elevated ALDH activity, may elucidate mechanisms for effective elimination of drug-resistant leukemic cells ex vivo and in vivo.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
0006-4971
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
76
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1209-13
pubmed:dateRevised
2007-11-15
pubmed:meshHeading
pubmed:year
1990
pubmed:articleTitle
Development and characterization of a cyclophosphamide-resistant subline of acute myeloid leukemia in the Lewis x Brown Norway hybrid rat.
pubmed:affiliation
Oncology Center, Johns Hopkins University School of Medicine, Baltimore, MD.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't