Journal Article

Organomagnesium suppresses inflammation-associated colon carcinogenesis in male Crj: CD-1 mice

Toshiya Kuno, Yuichiro Hatano, Hiroyuki Tomita, Akira Hara, Yoshinobu Hirose, Akihiro Hirata, Hideki Mori, Masaru Terasaki, Sonoko Masuda and Takuji Tanaka

in Carcinogenesis

Volume 34, issue 2, pages 361-369
Published in print February 2013 | ISSN: 0143-3334
Published online November 2012 | e-ISSN: 1460-2180 | DOI: http://dx.doi.org/10.1093/carcin/bgs348
Organomagnesium suppresses inflammation-associated colon carcinogenesis in male Crj: CD-1 mice

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Magnesium (Mg) deficiency increases genomic instability and Mg intake has been reported to be inversely associated with a risk of colorectal cancer (CRC). This study was designed to determine whether organo-Mg in drinking water suppresses inflammation-associated colon carcinogenesis in mice. Male Crj: CD-1 mice were initiated with a single i.p. injection of azoxymethane (AOM, 10mg/kg body weight) and followed by a 1 week exposure to dextran sulfate sodium (DSS, 1.5%, w/v) in drinking water to induce colonic neoplasms. They were then given the drinking water containing 7, 35 or 175 p.p.m. organo-Mg for 13 weeks. The chemopreventive efficacy of organo-Mg was determined 16 weeks after the AOM exposure. Administration with organo-Mg at all doses caused a significant inhibition of CRC development (P < 0.01 and P < 0.001). Especially, the highest dose of organo-Mg significantly suppressed the occurrence of all the colonic pathological lesions (mucosal ulcer, dysplasia, adenoma and adenocarcinoma). Organo-Mg also significantly reduced the number of mitoses/anaphase bridging, as well as proliferation of CRC. Additionally, at week 4, organo-Mg lowered the messenger RNA expression of certain proinflammatory cytokines, such as interleukin-1β, interleukin-6, interferon-γ and inducible nitric oxide synthase in the lesion-free colorectal mucosa at week 4 but increased the Nrf-2 messenger RNA expression. Our findings that organo-Mg inhibits inflammation-related mouse colon carcinogenesis by modulating the proliferative activities and chromosomal instability of CRC and suppressing colonic inflammation may suggest potential use of organo-Mg for clinical chemoprevention trials of CRC in the inflamed colon.

Journal Article.  5832 words.  Illustrated.

Subjects: Clinical Cytogenetics and Molecular Genetics

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