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Effects of dietary folate on intestinal tumorigenesis in the apcMin mouse.
Cancer Res 2000; 60(19):5434-40CR

Abstract

Dietary folate appears to be inversely related to colorectal cancer risk. This study investigated the effects of dietary intervention with folate or the development of intestinal polyps in Min (Apc +/-) mice. Weanling Mil mice were fed diets containing 0, 2 (basal requirement), 8, or 20 mg folate/kg diet. At 3 and 6 months of dietary intervention, 50% of the mice from each group were sacrificed, and the small intestine and colon were analyzed for polyps and aberrant crypt foci (ACF). Serum folate concentrations accurately reflected dietary folate levels (P < 0.001). At 3 months no significant difference in the average number of total small intestinal polyps was observed among the four groups. However, increasing dietary folate levels significantly reduced the number of ileal, but not duodenal or jejunal, polyps in a dose-dependent manner (P-trend = 0.001); folate supplementation at 20 mg/kg diet was associated with a 68-78% reduction in the number of ileal polyps compared with the other three diets (P < 0.007). The number of ileal polyps was inversely correlated with serum folate concentrations (P = 0.03). At 3 months, increasing dietary folate levels significantly decreased the number of colonic ACF in a dose-dependent manner (P = 0.05); the control and two folate supplemented diets significantly reduced the number of colonic ACF by 75 100% compared with the folate-deficient diet (P < 0.04). The number of colonic ACF was inversely correlated with serum folate concentration (P = 0.05). No significant difference in the number of colonic adenoma was observed among the four groups at 3 months. At 6 months, no significant differences in the average number of total small intestinal, duodenal, and jejunal polyps, colonic adenomas, and colonic ACF wer observed among the four groups. However, the folate-deficient diet had 62-76% lower number of ileal polyps compared with the control and two folate-supplemented diets (P < 0.003). Serum folate concentrations, but not dietary folate levels, were directly correlated with the number of ilea polyps (P = 0.006). These data suggest that dietary folate supplementation suppresses the development of ileal polyps and colonic ACF in this model However, at later time points, folate supplementation appears to have an opposite effect on ileal polyps. These data generally support the role of folate in intestinal tumorigenesis suggested in epidemiological studies and chemical carcinogen animal models. Notwithstanding the limitations associated with this model, these data suggest that the optimal timing and dose of folate intervention need to be determined for safe and effective folate chemoprevention.

Authors+Show Affiliations

Department of Medicine, University of Toronto, Ontario, Canada.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

11034085

Citation

Song, J, et al. "Effects of Dietary Folate On Intestinal Tumorigenesis in the apcMin Mouse." Cancer Research, vol. 60, no. 19, 2000, pp. 5434-40.
Song J, Medline A, Mason JB, et al. Effects of dietary folate on intestinal tumorigenesis in the apcMin mouse. Cancer Res. 2000;60(19):5434-40.
Song, J., Medline, A., Mason, J. B., Gallinger, S., & Kim, Y. I. (2000). Effects of dietary folate on intestinal tumorigenesis in the apcMin mouse. Cancer Research, 60(19), pp. 5434-40.
Song J, et al. Effects of Dietary Folate On Intestinal Tumorigenesis in the apcMin Mouse. Cancer Res. 2000 Oct 1;60(19):5434-40. PubMed PMID: 11034085.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Effects of dietary folate on intestinal tumorigenesis in the apcMin mouse. AU - Song,J, AU - Medline,A, AU - Mason,J B, AU - Gallinger,S, AU - Kim,Y I, PY - 2000/10/18/pubmed PY - 2001/2/28/medline PY - 2000/10/18/entrez SP - 5434 EP - 40 JF - Cancer research JO - Cancer Res. VL - 60 IS - 19 N2 - Dietary folate appears to be inversely related to colorectal cancer risk. This study investigated the effects of dietary intervention with folate or the development of intestinal polyps in Min (Apc +/-) mice. Weanling Mil mice were fed diets containing 0, 2 (basal requirement), 8, or 20 mg folate/kg diet. At 3 and 6 months of dietary intervention, 50% of the mice from each group were sacrificed, and the small intestine and colon were analyzed for polyps and aberrant crypt foci (ACF). Serum folate concentrations accurately reflected dietary folate levels (P < 0.001). At 3 months no significant difference in the average number of total small intestinal polyps was observed among the four groups. However, increasing dietary folate levels significantly reduced the number of ileal, but not duodenal or jejunal, polyps in a dose-dependent manner (P-trend = 0.001); folate supplementation at 20 mg/kg diet was associated with a 68-78% reduction in the number of ileal polyps compared with the other three diets (P < 0.007). The number of ileal polyps was inversely correlated with serum folate concentrations (P = 0.03). At 3 months, increasing dietary folate levels significantly decreased the number of colonic ACF in a dose-dependent manner (P = 0.05); the control and two folate supplemented diets significantly reduced the number of colonic ACF by 75 100% compared with the folate-deficient diet (P < 0.04). The number of colonic ACF was inversely correlated with serum folate concentration (P = 0.05). No significant difference in the number of colonic adenoma was observed among the four groups at 3 months. At 6 months, no significant differences in the average number of total small intestinal, duodenal, and jejunal polyps, colonic adenomas, and colonic ACF wer observed among the four groups. However, the folate-deficient diet had 62-76% lower number of ileal polyps compared with the control and two folate-supplemented diets (P < 0.003). Serum folate concentrations, but not dietary folate levels, were directly correlated with the number of ilea polyps (P = 0.006). These data suggest that dietary folate supplementation suppresses the development of ileal polyps and colonic ACF in this model However, at later time points, folate supplementation appears to have an opposite effect on ileal polyps. These data generally support the role of folate in intestinal tumorigenesis suggested in epidemiological studies and chemical carcinogen animal models. Notwithstanding the limitations associated with this model, these data suggest that the optimal timing and dose of folate intervention need to be determined for safe and effective folate chemoprevention. SN - 0008-5472 UR - https://www.unboundmedicine.com/medline/citation/11034085/Effects_of_dietary_folate_on_intestinal_tumorigenesis_in_the_apcMin_mouse_ L2 - http://cancerres.aacrjournals.org/cgi/pmidlookup?view=long&amp;pmid=11034085 DB - PRIME DP - Unbound Medicine ER -