Increased polyamine intake inhibits age-associated alteration in global DNA methylation and 1,2-dimethylhydrazine-induced tumorigenesis

• Published in: PloS one 2013-05, Vol.8 (5), p.e64357
• Main Authors: Soda, Kuniyasu, Kano, Yoshihiko, Chiba, Fumihiro, Koizumi, Kei, Miyaki, Yuichiro
• Format: Article
• Language: English
• Subjects: 1,2-Dimethylhydrazine; Age; Aging; Aging - genetics; Animals; Biology; Cell Line; Colon; Colon cancer; Colonic Neoplasms - drug therapy; Colonic Neoplasms - genetics; Deoxyribonucleic acid; Departments; Development and progression; Dimethylhydrazines; DNA; DNA (Cytosine-5-)-Methyltransferases; DNA methylation; DNA Methylation - drug effects; DNA methyltransferase; Genomes; Group dynamics; HT29 Cells; Humans; Inflammation; Intestine; Jurkat Cells; Laboratory animals; Male; Medicine; Methylation; Mice; Mice, Inbred BALB C; Nutrition research; Polyamines; Polyamines - metabolism; Polyamines - therapeutic use; Prostate; Spermidine; Spermine; Spermine - metabolism; Spermine - therapeutic use; Studies; Surgery; Tumorigenesis; Tumors
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0064357

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 Jc1:ICR 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 probability = 0.027, p = 0.025). 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, p = 0.039). Spermine seems to play important roles in inhibiting age-associated and polyamine-deficient induced abnormal gene methylation as well as pathological changes including tumorigenesis.