The rate of dihydrofolate reductase synthesis in the AT3000 line of methotrexate-resistant murine Sarcoma 180 cells is approximately 200to 250-fold greater than that of the sensitive, parental line. We have purified cDNA sequences complementary to dihydrofolate reductase mRNA and subsequently used this probe to quantitate dihydrofolate reductase mRNA and gene copies in each of these lines. Anal...

The rate of dihydrofolate reductase synthesis in the AT3000 line of methotrexate-resistant murine Sarcoma 180 cells is approximately 200to 250-fold greater than that of the sensitive, parental line. We have purified cDNA sequences complementary to dihydrofolate reductase mRNA and subsequently used this probe to quantitate dihydrofolate reductase mRNA and gene copies in each of these lines. Anal...

A fluorescent labeling technique has been devised to quantitate dihydrofolate reductase levels in individual cells and has been used to examine the heterogeneity in dihydrofolate reductase levels within various populations of methotrexate-resistant and parental cells. Precise quantitation of cellular dihydrofolate reductase levels in parental and methotrexate-resistant cells (having up to sever...

We have observed that rodent cell lines (mouse, hamster) contain approximately 10 times the levels of dihydrofolate reductase as human cell lines, yet the sensitivity to methotrexate (ED(50)), the folate antagonist that targets this enzyme, is similar. Our previous studies showed that dihydrofolate reductase protein levels increased after methotrexate exposure, and we proposed that this increas...

Previous investigations have suggested that high-dose methotrexate with leucovorin rescue is a potentially useful strategy for overcoming antifolate resistance. Interactions between methotrexate (MTX) and leucovorin and their respective metabolites appear to occur at multiple intracellular sites, including dihydrofolate reductase (MTX/MTX polyglutamates versus dihydrofolate) and other folate-de...

We compared the expression of dihydrofolate reductase minigenes with and without an intron. The levels of protein were significantly higher in the presence of dihydrofolate reductase intron 1. However, mRNA levels in both constructs were comparable. In addition, the RNA transcribed from either construct was correctly polyadenylated and exported to the cytoplasm. The intron-mediated increase in ...

Dihydrofolalate reductase (DHFR) inhibitors are of significant interest as potential tool against parasites and other microbial infections. Dihydrofolate reductase is a ubiquitous enzyme present in almost all eukaryotic and prokaryotic cells and has potential importance in biochemistry and medicinal chemistry. It catalyses the various biochemical reactions are of vital importance, inhibition of...

By recombination between bacteriophage T4 wh2, a dihydrofolate reductaseless mutant, and T6, I have prepared T4 wh(T6), a T4 strain which codes for the T6-specific soluble dihydrofolate reductase. This strain has the heat sensitivity of T6, not T4, which provides direct evidence that the wh gene codes for both the soluble dihydrofolate reductase and the structural dihydrofolate reductase which ...

Folic acid supplementation may meliorate cardiovascular disease risk by improving vascular endothelial structure and function. However, the underlying mechanisms are still lack of a global understanding. To be used, folic acid must be converted to 7,8-dihydrofolate by dihydrofolate reductase to generate one-carbon derivatives serving as important cellular cofactors in the synthesis of nucleotid...