title: Increased polyamine intake inhibits age-associated alteration in global DNA methylation and 1,2-dimethylhydrazine-induced tumorigenesis.
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 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.
authors.affiliation: Department of Cardiovascular Research Institute, Saitama Medical Center, Jichi Medical University, Saitama-city, Saitama, Japan. soda@jichi.ac.jp
authors.forename: Kuniyasu
authors.initials: K
authors.lastname: Soda
authors.forename: Yoshihiko
authors.initials: Y
authors.lastname: Kano
authors.forename: Fumihiro
authors.initials: F
authors.lastname: Chiba
authors.forename: Kei
authors.initials: K
authors.lastname: Koizumi
authors.forename: Yuichiro
authors.initials: Y
authors.lastname: Miyaki
mesh_terms: D000375:Aging / Q000235:genetics*; D000818:Animals; D002460:Cell Line; D003110:Colonic Neoplasms / Q000188:drug therapy / Q000235:genetics; D004248:DNA (Cytosine-5-)-Methyltransferases; D019175:DNA Methylation / Q000187:drug effects*; D019073:HT29 Cells; D006801:Humans; D019169:Jurkat Cells; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D011073:Polyamines / Q000378:metabolism* / Q000627:therapeutic use*; D013096:Spermine / Q000378:metabolism / Q000627:therapeutic use
chemical_list: D011073:Polyamines; D013096:Spermine; D004248:DNA (Cytosine-5-)-Methyltransferases