title: Organomagnesium suppresses inflammation-associated colon carcinogenesis in male Crj: CD-1 mice.
abstract: 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.
authors.affiliation: Department of Tumor Pathology, Gifu University Graduate School of Medicine, 1-1 Yanagido,  Gifu 501-1194, Japan.
authors.forename: Toshiya
authors.initials: T
authors.lastname: Kuno
authors.forename: Yuichiro
authors.initials: Y
authors.lastname: Hatano
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Tomita
authors.forename: Akira
authors.initials: A
authors.lastname: Hara
authors.forename: Yoshinobu
authors.initials: Y
authors.lastname: Hirose
authors.forename: Akihiro
authors.initials: A
authors.lastname: Hirata
authors.forename: Hideki
authors.initials: H
authors.lastname: Mori
authors.forename: Masaru
authors.initials: M
authors.lastname: Terasaki
authors.forename: Sonoko
authors.initials: S
authors.lastname: Masuda
authors.forename: Takuji
authors.initials: T
authors.lastname: Tanaka
mesh_terms: D000230:Adenocarcinoma / Q000139:chemically induced / Q000276:immunology / Q000517:prevention & control*; D000236:Adenoma / Q000139:chemically induced / Q000276:immunology / Q000517:prevention & control*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001397:Azoxymethane / Q000633:toxicity; D015153:Blotting, Western; D002273:Carcinogens / Q000633:toxicity; D049109:Cell Proliferation / Q000187:drug effects; D002471:Cell Transformation, Neoplastic / Q000187:drug effects*; D003092:Colitis / Q000139:chemically induced / Q000276:immunology / Q000517:prevention & control*; D003110:Colonic Neoplasms / Q000139:chemically induced / Q000276:immunology / Q000517:prevention & control*; D016264:Dextran Sulfate / Q000633:toxicity; D006801:Humans; D007124:Immunoenzyme Techniques; D007249:Inflammation / Q000139:chemically induced / Q000276:immunology / Q000517:prevention & control*; D007371:Interferon-gamma / Q000235:genetics / Q000378:metabolism; D053583:Interleukin-1beta / Q000235:genetics / Q000378:metabolism; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism; D017616:Magnesium Compounds / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D008940:Mitotic Index; D009942:Organometallic Compounds / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured
chemical_list: D002273:Carcinogens; D053583:Interleukin-1beta; D015850:Interleukin-6; D017616:Magnesium Compounds; D009942:Organometallic Compounds; D012333:RNA, Messenger; D011994:Recombinant Proteins; C554125:interferon gamma-1b; D007371:Interferon-gamma; D016264:Dextran Sulfate; D001397:Azoxymethane