Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
1994-11-9
pubmed:abstractText
This report describes the intracellular metabolism of 5-methyltetrahydrofolate (5-methyl-H4PteGlu) and 5-formyltetrahydrofolate (5-formyl-H4PteGlu) to the various folate forms and their respective polyglutamated states in the MCF-7 human breast-cancer cell line. The intracellular folate distribution observed in MCF-7 cells treated with 5-methyl-H4PteGlu was similar to that seen in cells treated with 5-formyl-H4PteGlu. In cells exposed to 5-formyl-H4PteGlu for 24 h, the folate pool consisted of 103 +/- 10 pmol/mg 10-formyl-H4PteGlu, 120 +/- 18 pmol/mg H4PteGlu, and 71 +/- 18 pmol/mg 5-methyl-H4PteGlu versus 88 +/- 5, 54 +/- 20 and 87 +/- 10 pmol/mg, respectively, for cells exposed to 5-methyl-H4PteGlu. Only the difference seen in H4PteGlu levels between cells exposed to either 5-methyl-H4PteGlu or 5-formyl-H4PteGlu reached statistical significance (P < 0.05). In the absence of vitamin B12, exposure to 5-methyl-H4PteGlu resulted in 154 +/- 17 pmol/mg 5-methyl-H4PteGlu along with only 8 +/- 5 pmol/mg 10-formyl-H4PteGlu and 4 +/- 2 pmol/mg H4PteGlu, thus demonstrating the marked dependence on vitamin B12 for the metabolism of 5-methyl-H4PteGlu to the other intracellular folates. 5-10-Methylene- H4PteGlu (2 +/- 1.3 pmol/mg) was detected only in cells exposed to 5-formyl-H4PteGlu for 24 h, not in cells treated with 5-methyl-H4PteGlu. The profile of polyglutamates detected in cells treated with either 5-formyl-H4PteGlu or 5-methyl-H4PteGlu for 24 h was not significantly different, although cells treated with 5-methyl-H4PteGlu tended to have less conversion to the higher polyglutamates (Glu3-Glu5) as compared with those treated with 5-formyl-H4PteGlu. In 5-methyl-H4PteGlu-treated cells grown in the absence of vitamin B12, the pentaglutamate was the only polyglutamate form detected, accounting for only 11% of the total folate pool. Since there does not appear to be a greater formation of the optimal reduced-folate forms necessary to achieve enhanced thymidylate synthase (TS) inhibition through ternary-complex formation in cells exposed to 5-methyl-H4PteGlu versus 5-formyl-H4PteGlu, these studies suggest that the use of 5-methyl-H4PteGlu would not be advantageous over that of 5-formyl-H4PteGlu in combination regimens with the fluoropyrimidines.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:issn
0344-5704
pubmed:author
pubmed:issnType
Print
pubmed:volume
34
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
491-6
pubmed:dateRevised
2004-11-17
pubmed:meshHeading
pubmed:year
1994
pubmed:articleTitle
Intracellular metabolism of 5-methyltetrahydrofolate and 5-formyltetrahydrofolate in a human breast-cancer cell line.
pubmed:affiliation
NCI-Navy Medical Oncology Branch, National Cancer Institute, Bethesda, MD 20889.
pubmed:publicationType
Journal Article