Increased uracil misincorporation in lymphocytes from folate-deficient rats

The development of certain human cancers has been linked with inadequate in take of folates. The effects of folate deficiency in vivo on DNA stability (strand breakage, misincorporated uracil and oxidative base damage) in lymp hocytes isolated from rats fed a diet deficient in folic acid was determine d. Because the metabolic pathways of folate and other methyl donors are clo sely coupled, the effects of methionine and choline deficiency alone or in combination with folate deficiency were determined. Feeding male Hooded Lis ter rats a folate-free diet for 10 weeks created a moderate relate deficien cy (25-50% (approx.) decrease in plasma, red blood cell and hepatic folate concentrations (P < 0.05) and a 20% rise in plasma homocysteine (P < 0.05)) . Lymphocyte DNA strand breakage was increased successively in all groups a fter 4 weeks and 8 weeks on the diet (50-100% (approx.) after 8 weeks). Onl y low folate specifically and progressively induced uracil misincorporation throughout the study (100% (approx.) after 8 weeks). Neither folate defici ency nor choline/methionine deficiency altered oxidative DNA base damage. i n summary, moderate folate deficiency in vivo is associated with a decrease in DNA stability, measured as increased DNA strand breakage and misincorpo rated uracil. (C) 2000 Cancer Research Campaign http://www.bjcancer.com.