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: Toshiya Kuno, Yuichiro Hatano, Hiroyuki Tomita, Akira Hara, Yoshinobu Hirose, Akihiro Hirata, Hideki Mori, Masaru Terasaki, Sonoko Masuda, Takuji Tanaka
• Journal: Carcinogenesis (Carcinogenesis) Vol. 34 Issue 2 Pg. 361-9 (Feb 2013) ISSN: 1460-2180 [Electronic] England
• PMID: 23125223 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Carcinogens
• Interleukin-1beta
• Interleukin-6
• Magnesium Compounds
• Organometallic Compounds
• RNA, Messenger
• Recombinant Proteins
• interferon gamma-1b
• Interferon-gamma
• Dextran Sulfate
• Azoxymethane

Topics

• Adenocarcinoma (chemically induced, immunology, prevention & control)
• Adenoma (chemically induced, immunology, prevention & control)
• Animals
• Apoptosis (drug effects)
• Azoxymethane (toxicity)
• Blotting, Western
• Carcinogens (toxicity)
• Cell Proliferation (drug effects)
• Cell Transformation, Neoplastic (drug effects)
• Colitis (chemically induced, immunology, prevention & control)
• Colonic Neoplasms (chemically induced, immunology, prevention & control)
• Dextran Sulfate (toxicity)
• Humans
• Immunoenzyme Techniques
• Inflammation (chemically induced, immunology, prevention & control)
• Interferon-gamma (genetics, metabolism)
• Interleukin-1beta (genetics, metabolism)
• Interleukin-6 (genetics, metabolism)
• Magnesium Compounds (pharmacology)
• Male
• Mice
• Mice, Inbred ICR
• Mitotic Index
• Organometallic Compounds (pharmacology)
• RNA, Messenger (genetics)
• Real-Time Polymerase Chain Reaction
• Recombinant Proteins (genetics, metabolism)
• Reverse Transcriptase Polymerase Chain Reaction
• Tumor Cells, Cultured