Indispensable Folic Acid

Ames Group Discovers How Inadequate Folate Causes DNA Damage

by Robert Sanders

Researchers at Berkeley have discovered how folic acid deficiency leads to DNA damage, emphasizing the dietary importance of this B vitamin in reducing the risk of heart disease, cancer and even brain damage.

The study also showed that for people deficient in folic acid, supplementing the diet with folic acid can reduce DNA damage.

Folic acid or folate is found in abundance in leafy green vegetables and fruit-orange juice is a good source-and has long been recognized as an essential micronutrient in the diet.

Despite this, 10 percent of the population and an estimated 50 percent of some low-income minority populations have a folic acid deficiency. Folic acid deficiency has been linked in various studies to an increased risk of heart disease, cancer and various types of brain dysfunction. In addition, pregnant women are urged to take folic acid supplements to reduce the risk of neural tube defects such as spina bifida.

Until now, however, how folic acid deficiency causes such problems has been poorly understood.

"We've now worked out the mechanism by which this happens," said Bruce Ames, professor of biochemistry and molecular biology.

Researchers have shown that in folate deficiency, synthesis of the DNA base thymine from its precursor, uracil, is inhibited, causing uracil to accumulate in the cell. Ames and his team suspected that such conditions make cells misincorporate uracil into their DNA in place of thymine, and that in removing uracil from DNA the cells' built-in repair system sometimes creates breaks in both the DNA and chromosomes. Such breaks could lead to cancer and various other diseases.

To test this hypothesis, Ames and his colleagues Ben Blount, then a graduate student and now at the Centers for Disease Control and Prevention in Atlanta; and Matthew Mack, a postdoctoral researcher here, developed a way to detect uracil misincorporation into DNA.

Their study, reported in the April 1 issue of the Proceedings of the National Academy of Sciences, confirmed the hypothesis. In a group of human volunteers with folic acid deficiency they found massive incorporation of uracil into DNA and subsequent chromosome breaks.



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