Maternal B vitamin supplementation from preconception through weaning suppresses intestinal tumorigenesis in Apc1638N mouse offspring.
Gut
; 60(12): 1695-702, 2011 Dec.
Article
em En
| MEDLINE
| ID: mdl-21659408
ABSTRACT
OBJECTIVE:
Variations in the intake of folate are capable of modulating colorectal tumorigenesis; however, the outcome appears to be dependent on timing. This study sought to determine the effect of altering folate (and related B vitamin) availability during in-utero development and the suckling period on intestinal tumorigenesis.DESIGN:
Female wildtype mice were fed diets either mildly deficient, replete or supplemented with vitamins B(2), B(6), B(12) and folate for 4 weeks before mating to Apc(1638N) males. Females remained on their diet throughout pregnancy and until weaning. After weaning, all Apc(1638N) offspring were maintained on replete diets for 29 weeks.RESULTS:
At 8 months of age tumour incidence was markedly lower among offspring of supplemented mothers (21%) compared with those of replete (59%) and deficient (55%) mothers (p=0.03). Furthermore, tumours in pups born to deficient dams were most likely to be invasive (p=0.03). The expression of Apc, Sfrp1, Wif1 and Wnt5a--all of which are negative regulatory elements of the Wnt signalling cascade--in the normal small intestinal mucosa of pups decreased with decreasing maternal B vitamin intake, and for Sfrp1 this was inversely related to promoter methylation. ß-Catenin protein was elevated in offspring of deficient dams.CONCLUSIONS:
These changes indicate a de-repression of the Wnt pathway in pups of deficient dams and form a plausible mechanism by which maternal B vitamin intake modulates tumorigenesis in offspring. These data indicate that maternal B vitamin supplementation suppresses, while deficiency promotes, intestinal tumorigenesis in Apc(1638N) offspring.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Efeitos Tardios da Exposição Pré-Natal
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Complexo Vitamínico B
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Deficiência de Vitamina D
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Neoplasias Colorretais
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Suplementos Nutricionais
Tipo de estudo:
Etiology_studies
Limite:
Animals
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Female
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Humans
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Male
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Pregnancy
Idioma:
En
Revista:
Gut
Ano de publicação:
2011
Tipo de documento:
Article