Linked Life Data

2452889

Source:http://linkedlifedata.com/resource/pubmed/id/2452889

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
7
pubmed:dateCreated
1988-6-20
pubmed:abstractText
The 1-isoquinolylmethylene derivative of N-hydroxy-N'-aminoguanidine (HAG) is the most potent agent of the recently synthesized series of HAG-derived ribonucleotide reductase inhibitors. To potentiate the effects of the HAG-isoquinoline drug [HAG-1-isoquinolylmethylene tosylate (HAG-IQ)], we combined it with other inhibitors of ribonucleotide reductase. Using mouse leukemia L1210 cell cultures, we tested drug combinations for their cytostatic and cytotoxic properties and for their effects on intracellular ribonucleotide reductase activity and nucleic acid synthesis. Deoxyguanosine or deoxyadenosine combined with HAG-IQ inhibited cell growth in an additive manner; three-drug combinations, HAG-IQ plus either deoxyguanosine/8-aminoguanosine or deoxyadenosine/deoxycoformycin, were strongly synergistic. When Desferal, an iron chelator, was added to these combinations, the four-drug combinations increased inhibition of cell growth and increased cytotoxicity. The intracellular target of these drug combinations in L1210 cells was the ribonucleotide reductase site. The formation of deoxycytidine from [14C]cytidine and incorporation into DNA were markedly inhibited by these drug combinations, while RNA synthesis was unaffected. These data show that the antiproliferative and cytotoxic effects of HAG-IQ, a potent inhibitor by itself, can be further potentiated in combinations with other ribonucleotide reductase inhibitors.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
0027-8874
pubmed:author
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
80
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
491-6
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
1988
pubmed:articleTitle
Effects of N-hydroxy-N'-aminoguanidine isoquinoline in combination with other inhibitors of ribonucleotide reductase on L1210 cells.
pubmed:affiliation
Department of Internal Medicine, University of South Florida, College of Medicine, Tampa 33612.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't