Epithelial cells folic acid

The surface epithelial cells of the small intestine are renewed rapidly and regularly. It takes about two days for the cells of the duodenum to be renewed completely. As a result of its rapid renewal rate, the intestinal epithelium is susceptible to various factors that may influence proliferation. Exposure of the intestine to ionizing radiation and cytotoxic drugs (such as folic acid antagonists and colchicine) reduces the cell renewal rate. 

In summary, DNA synthesis requires synthesis of dTMP and the purines adenine and guanine. THF, derived from the vitamin folic acid, is required for the biosynthesis of these nucleotides. Treatment with methotrexate blocks the cell s ability to regenerate THF, leading to inhibition of these biosynthetic pathways. The lack of nucleotides prevents DNA synthesis, and these cancer cells cannot divide without DNA synthesis. Unfortunately, the effects of methotrexate are nonspecific and other rapidly dividing cells such as epithelial cells in the oral cavity, intestine, skin, and blood cells are also inhibited. This leads to the side effects associated with methotrexate (and other cancer chemotherapy drugs) such as mouth sores, low white blood cell counts, stomach upset, hair loss, skin rashes, and itching. 

Folic acid, also called folate, is essential for transferring one-carbon units involved in phospholipid, DNA/RNA, protein and neurotransmitter syntheses (Selhub and Rosenberg 1996). Furthermore folate is an essential dietary component for the formation of red and white blood cells and the epithelial cells in the digestive tract (Gregory et al. 1984). 

There are also marked changes in blood pressure and cardiac contracture (Jenkins and Spector, 1973). A major concern is folic acid-induced toxicity of the kidneys. Large doses of folic acid in animals cause immediate increase in DNA synthesis, total protein with hypertrophy, and hyperplasia of the kidney epithelial cells (Threlfall, 1968 Threlfall et al, 1967 Tilson, 1970). 

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