Increased polyamine intake inhibits age-associated alteration in global DNA methylation and 1,2-dimethylhydrazine-induced tumorigenesis.
PLoS One
; 8(5): e64357, 2013.
Article
em En
| MEDLINE
| ID: mdl-23696883
ABSTRACT
Polyamines (spermine and spermidine) play many important roles in cellular function and are supplied from the intestinal lumen. We have shown that continuous high polyamine intake inhibits age-associated pathologies in mice. The mechanism by which polyamines elicit these effects was examined. Twenty-four week old Jc1ICR male mice were fed one of three experimental chows containing different polyamine concentrations. Lifetime intake of high polyamine chow, which had a polyamine content approximately three times higher than regular chow, elevated polyamine concentrations in whole blood, suppressed age-associated increases in pro-inflammatory status, decreased age-associated pathological changes, inhibited age-associated global alteration in DNA methylation status and reduced the mortality in aged mice. Exogenous spermine augmented DNA methyltransferase activity in Jurkat and HT-29 cells and inhibited polyamine deficiency-induced global alteration in DNA methylation status in vitro. In addition, increased polyamine intake was associated with a decreased incidence of colon tumors in BALB/c mice after 1,2-demethylhydrazine administration; 12 mice (60%) in the low polyamine group developed tumors, compared with only 5 mice (25%) in the high polyamine group (Fisher's exact probabilityâ=â0.027, pâ=â0.025). However, increased polyamine intake accelerated the growth of established tumors; maximal tumor diameter in the Low and High groups was 3.85±0.90 mm and 5.50±1.93 mm, respectively (Mann-Whitney test, pâ=â0.039). Spermine seems to play important roles in inhibiting age-associated and polyamine-deficient induced abnormal gene methylation as well as pathological changes including tumorigenesis.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Contexto em Saúde:
6_ODS3_enfermedades_notrasmisibles
Problema de saúde:
6_colon_rectum_cancers
Assunto principal:
Poliaminas
/
Envelhecimento
/
Metilação de DNA
Tipo de estudo:
Risk_factors_studies
Limite:
Animals
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Humans
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Male
Idioma:
En
Revista:
PLoS One
Assunto da revista:
CIENCIA
/
MEDICINA
Ano de publicação:
2013
Tipo de documento:
Article
País de afiliação:
Japão