Association of Marginal Folate Depletion With Increased Human Chromosomal Damage In Vivo: Demonstration by Analysis of Micronucleated Erythrocytes

Folate deficiency causes uracil misincorporation into human DNA and chromosome breakage: Implications for cancer and neuronal damage

“…Squares represent individuals with deficient erythrocyte folate levels but borderline plasma folate levels (6 ng͞ml Ն plasma folate Ն4 ng͞ml). Triangles are averaged values before and after supplementation of an individual with Crohn disease (19). (A) Uracil levels before and after folate supplementation (5 mg per day).…”

“…Blood samples were taken at the beginning and at 6, 7, and 8 weeks after daily supplementation with 5 mg of folic acid. Additional data were obtained from a splenectomized individual with Crohn disease (19). Frozen blood samples from this individual before and after supplementation with folinic acid (25 mg per day) and folic acid (15 and 5 mg per day) were obtained and analyzed for DNA uracil content.…”

“…The quarter of the population with the lowest fruit and vegetable intake has about twice the risk of developing most types of cancers as the quarter with the highest intake (13)(14)(15). Folate deficiency in humans induces extensive chromosome damage (16), fragile site expression (17), micronucleus formation (18,19), and increased uracil levels in bone marrow cell DNA (20).…”

Interactions Between MTHFR C677T - A1298C Variants and Folic Acid Deficiency Affect Breast Cancer Risk in a Chinese Population

“…FA deficiency induces deficient methylation of deoxyuridylic acid (dUMP) to deoxythymidylic acid (dTMP) leading to uracil misincorporation (Fenech, 2001;Mazz et al, 2010) and DNA global hypomethylation (Rampersaud et al, 2000); this not only leads to point mutations, the generation of single-and double-stranded DNA breaks, chromosome breakage, micronucleus formation and abnormal apoptosis (Everson et al, 1988;Fenech et al, 2001;Fenech et al, 2002;Eichholzer et al, 2006;Yang et al, 2008;Mazz et al, 2010;Bouckaert et al, 2011), but also may…”

The causes and prevention of cancer: gaining perspective.

“…Folic acid may be particularly important. Low folic acid intake causes chromosome breaks in rodents (25) and in humans (26,27) and increases tumor incidence in some rodent models (28). Folic acid is essential for the synthesis of DNA.…”