Linked Life Data

2942201

Source:http://linkedlifedata.com/resource/pubmed/id/2942201

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
1986-9-17
pubmed:abstractText
We studied the folate requirements of a human acute lymphoblastic leukemia cell line, MOLT-3, and methotrexate (MTX)-resistant sublines established in vitro. The requirement of pteroylglutamate (PGA) for optimal cell growth was different for each cell line. With increasing MTX resistance, there was progressive increase in PGA requirements, moving the PGA concentration-cell growth curve (dose-response curve) 1 log order of magnitude to the right. The increases in the requirement of 5-methyltetrahydrofolate (5-methyl-THF) by the resistant sublines were more pronounced than PGA requirement, moving the dose-response curve nearly 3 log orders in magnitude to the right. The concentrations in vitro of 5-methyl-THF required for optimal growth of the MTX-resistant sublines far exceeded the normal serum 5-methyl-THF concentrations known in humans. These observations show that MTX-resistant cell established in vitro in culture media containing PGA instead of 5-methyl-THF, a physiological folate, cannot be expected to grow in vivo. The collateral sensitivity of transport-impaired MTX-resistant sublines to 2,4-diamino-5-methyl-6-[(3',4',5'- trimethoxyanilino) methyl] quinazoline (trimetrexate, TMQ) was negated in the absence of PGA. With the addition of 5-methyl-THF, the parent cells became more resistant than the transport-impaired sublines to TMQ These data indicate that the collateral sensitivity of MTX resistant cells to the substituted 2,4-diaminoquinazoline is due to functional folate deficiency by virtue of the impaired transport of folate.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
0006-4971
pubmed:author
pubmed:issnType
Print
pubmed:volume
68
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
586-91
pubmed:dateRevised
2007-11-15
pubmed:meshHeading
pubmed:year
1986
pubmed:articleTitle
Folate requirements of methotrexate-resistant human acute lymphoblastic leukemia cell lines.
pubmed:publicationType
Journal Article, Comparative Study, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't