Molecular Nutrition

Folate supplementation differently affects uracil content in DNA in the mouse colon and liver

Kyong-Chol Kim^a1, Hyeran Jang^a2, Julia Sauer^a2, Ella M. Zimmerly^a2, Zhenhua Liu^a2, Aurelie Chanson^a2, Donald E. Smith^a3, Simonetta Friso^a4 and Sang-Woon Choi^a2 c1

^a1 Department of Family Medicine, Mizmedi Hospital, Seoul, South Korea

^a2 Vitamins and Carcinogenesis Laboratory, Jean Mayer USDA Human Nutrition Research Center on Aging, Tufts University, 711 Washington Street, Boston, MA 02111, USA

^a3 Comparative Biology Unit, Jean Mayer USDA Human Nutrition Research Center on Aging, Tufts University, 711 Washington Street, Boston, MA 02111, USA

^a4 University of Verona School of Medicine, Verona, Italy

Abstract

High folate intake may increase the risk of cancer, especially in the elderly. The present study examined the effects of ageing and dietary folate on uracil misincorporation into DNA, which has a mutagenic effect, in the mouse colon and liver. Old (18 months; n 42) and young (4 months; n 42) male C57BL/6 mice were pair-fed with four different amino acid-defined diets for 20 weeks: folate deplete (0 mg/kg diet); folate replete (2 mg/kg diet); folate supplemented (8 mg/kg diet); folate deplete (0 mg/kg diet) with thymidine supplementation (1·8 g/kg diet). Thymidylate synthesis from uracil requires folate, but synthesis from thymidine is folate independent. Liver folate concentrations were determined by the Lactobacillus casei assay. Uracil misincorporation into DNA was measured by a GC/MS method. Liver folate concentrations demonstrated a stepwise increase across the spectrum of dietary folate levels in both old (P = 0·003) and young (P < 0·001) mice. Uracil content in colonic DNA was paradoxically increased in parallel with increasing dietary folate among the young mice (P trend = 0·033), but differences were not observed in the old mice. The mean values of uracil in liver DNA, in contrast, decreased with increasing dietary folate among the old mice, but it did not reach a statistically significant level (P < 0·1). Compared with the folate-deplete group, thymidine supplementation reduced uracil misincorporation into the liver DNA of aged mice (P = 0·026). The present study suggests that the effects of folate and thymidine supplementation on uracil misincorporation into DNA differ depending on age and tissue. Further studies are needed to clarify the significance of increased uracil misincorporation into colonic DNA of folate-supplemented young mice.

(Received May 20 2010)

(Revised September 13 2010)

(Accepted September 24 2010)

(Online publication January 21 2011)

Key Words:

• Folate;
• Uracil;
• Thymidine;
• Colon;
• Liver;
• Mice

Correspondence:

^c1 Corresponding author: Dr S.-W. Choi, email sang.choi@tufts.edu