Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:dateCreated
1994-7-22
pubmed:abstractText
The fidelity and progression of DNA synthesis is critically dependent on the correct balance and availability of the deoxynucleoside triphosphate (dNTP) precursors for the polymerases involved in DNA replication and repair. Because folate-derived one-carbon groups are essential for the de novo synthesis of both purines and pyrimidines, the purpose of this study was to determine the effect of folate deprivation on deoxynucleotide pool levels and cell cycle progression. Primary cultures of phytohemagglutin (PHA)-stimulated splenocytes were used as the cellular model. T-cells and macrophages were purified from spleen cell suspensions obtained from F344 rats and recombined in culture. The cells were harvested after a 66-hr incubation with PHA and analyzed for nucleotide levels by reverse-phase HPLC with diode array detection. The proportion of cells in the different phases of the cell cycle was determined by bivariate flow cytometric measurement of bromodeoxyuridine (BrdU) incorporation and DNA content (propidium iodide staining). PHA-stimulated T-cells cultured in medium lacking folate and methionine manifested significant decreases in the deoxynucleotides dCTP, dTMP, dGTP, and dATP relative to cells cultured in complete medium. The reduction in dNTP pools was associated with a decrease in the corresponding ribonucleotide pools. Flow cytometric analysis revealed a 2-fold increase in S and G2/mitosis (G2/M) DNA content in PHA-stimulated cells cultured in the medium lacking folate and methionine, which suggests a delay in cell cycle progression. These alterations in DNA content were accompanied by a 5-fold decrease in BrdU incorporation relative to PHA-stimulated cells cultured in complete medium.(ABSTRACT TRUNCATED AT 250 WORDS)
pubmed:commentsCorrections
http://linkedlifedata.com/resource/pubmed/commentcorrection/8013406-1812810, http://linkedlifedata.com/resource/pubmed/commentcorrection/8013406-2369732, http://linkedlifedata.com/resource/pubmed/commentcorrection/8013406-2647496, http://linkedlifedata.com/resource/pubmed/commentcorrection/8013406-2784833, http://linkedlifedata.com/resource/pubmed/commentcorrection/8013406-2954951, http://linkedlifedata.com/resource/pubmed/commentcorrection/8013406-3096753, http://linkedlifedata.com/resource/pubmed/commentcorrection/8013406-3134613, http://linkedlifedata.com/resource/pubmed/commentcorrection/8013406-3292903, http://linkedlifedata.com/resource/pubmed/commentcorrection/8013406-3292906, http://linkedlifedata.com/resource/pubmed/commentcorrection/8013406-3292907, http://linkedlifedata.com/resource/pubmed/commentcorrection/8013406-3393163, http://linkedlifedata.com/resource/pubmed/commentcorrection/8013406-3691495, http://linkedlifedata.com/resource/pubmed/commentcorrection/8013406-3812550, http://linkedlifedata.com/resource/pubmed/commentcorrection/8013406-3888183, http://linkedlifedata.com/resource/pubmed/commentcorrection/8013406-4526300, http://linkedlifedata.com/resource/pubmed/commentcorrection/8013406-4587740, http://linkedlifedata.com/resource/pubmed/commentcorrection/8013406-7158770, http://linkedlifedata.com/resource/pubmed/commentcorrection/8013406-7350200
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
0091-6765
pubmed:author
pubmed:issnType
Print
pubmed:volume
101 Suppl 5
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
173-8
pubmed:dateRevised
2009-11-18
pubmed:meshHeading
pubmed:year
1993
pubmed:articleTitle
The essentiality of folate for the maintenance of deoxynucleotide precursor pools, DNA synthesis, and cell cycle progression in PHA-stimulated lymphocytes.
pubmed:affiliation
National Center for Toxicological Research, Jefferson, AR 72079.
pubmed:publicationType
Journal Article, In Vitro