Tumours folic acid

These are pyrimidine derivatives and are effective because of differences in susceptibility between the enzymes in humans and in the infective organism. Anticancer agents based on folic acid, e.g. methotrexate, inhibit dihydrofolate reductase, but they are less selective than the antimicrobial agents and rely on a stronger binding to the enzyme than the natural substrate has. They also block pyrimidine biosynthesis. Methotrexate treatment is potentially lethal to the patient, and is usually followed by rescue with folinic acid (A -formyl-tetrahydrofolic acid) to counteract the folate-antagonist action. The rationale is that folinic acid rescues normal cells more effectively than it does tumour cells. 

The main folate antagonist is methotrexate, an analogue of folic acid. Methotrexate competitively inhibits dihydrofolate reductase, the enzyme responsible for the synthesis of purine and pyramidine from folic acid. Trimetrexate, a methotrexate analogue, is useful in treating methotrexate-resistant tumours. It is also used to treat Pneumocystis carinii infections. Methotrexate is usually given orally, but may also be given intravenously or intrathecally. In addition to its use in cancer therapy, it is used in the treatment of psoriasis. Methotrexate can cause an obstructive nephropathy due to its precipitation in the renal calyx. 

Imprecisely diagnosed megaloblastic anaemia is the principal contraindication. Tumour cell proliferation in some cancers may be folate dependent and folic acid should be used in malignant disease only where there is confirmed folate deficiency anaemia. 

Methotrexate is used as an oral anticancer agent, but resistance may develop in tumour cells, and there are a number of unwanted side-effects. It has a high affinity for the mammalian form of dihydrofolate reductase and cannot be used as an antibacterial or antimalarial drug. After use at high doses in humans, the extent of depletion of folic acid may be such, that rescue with administration of folinic acid (a form of tetrahydrofolate) is necessary. 

Folic acid is required for growth, and the growth of tumours can be inhibited by using cancer treatment drugs which reduce... 

This efficient and facile synthesis combined with uptake in folic acid receptor expressing KB cells and tumour targetting in mice confirms the promise of this procedure. 

An improperly balanced diet may cause mutations and chromosomal aberrations. For the development of methods to counteract such changes, it is vital to determine the possible correlations between the dietary components and DNA changes. Folic acid and vitamin B12 are crucial elements in the methy-lation of DNA, proteins and neurotransmitiers. The development of neural tube defects associated with folic acid deficiency is related to methylation dysfunction and a malfunctioning expression of the genes responsible for the tube formation. Furthermore, it is believed that DNA hypermethylation causes mutations related to tumor initiation or development. Previous observations have shown that diets supplemented with the B group vitamins for 15 years were correlated with a significant reduction in the development of tumour diseases (Fenech 2001). 

It is not uncommon to prescribe folic acid to patients on AEDs. Doses from 0.2 to 15 mg folic acid per day have been recommended. However, pharmacological doses of folic acid may be associated with adverse effects, such as increased incidence of tumours. Doses of folic acid above 0.4 mg may cause the absorption of unmetabolized folic acid that can be detected in the circulation for several hours after intake. Furthermore, high doses of folic may increase the breakdown rate of some AEDs such as PHT. The serum concentrations of PHT may drop significantly when folic acid is introduced and seizures may be aggravated. It has been suggested that high doses of folic acid may have direct effects on the nervous system and cause seizures. However, there is no indication that this is a problem in patients with epilepsy and folic acid is not contraindicated for this reason (Moore 2005). 

Tumours The association between intakes of folate, vitamin Bs and vitamin B12 and the risk of colorectal cancer in women has been examined. Food fortification with folic acid for 3-9 years was associated with an increased risk... 

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