The role of DNA methylation in cadmium-induced anti-carcinogenesis

• Project/Area Number: 19590131
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Environmental pharmacy
• Research Institution: Hiroshima International University
• Principal Investigator: TAKIGUCHI Masufumi Hiroshima International University, 薬学部, 准教授 (90330753)
• Project Period (FY): 2007 – 2009
• Project Status: Completed (Fiscal Year 2009)
• Budget Amount: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2009: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2008: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2007: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: カドミウム / エピジェネティックス / がん / DNA / メチル化 / 抗がん / MMP / メタロチオネイン / DNAメチル化 / エピジェネティック / DNAメチル化酵素 / 亜鉛

Research Abstract

Cadmium (Cd) is a carcinogenic metal in humans and rodents. Cd in certain instances can also be anti-carcinogenic. In this study, Cd is an effective inhibitor of DNA methyltransferase, controlled DNA methylation status, and kinetic studies indicated the mechanism is via interference with enzyme-DNA interaction. The enzyme-DNA binding site may be Pro-Cys in catalytic site of enzyme. In addition, Cd inhibited cell invasion activity via inhibition of MMP2 activity. This result proposed one of the new mechanisms of cadmium-induced anti-carcinogenesis.

Research Products

• [Journal Article] Masao Sato Tissue-dependent preventive effect of metallothionein against DNA damage in dyslipidemic mice under repeated stresses of fasting or restraint. (2009)
  • Author(s): Minoru Higashimoto, Naoki Isoyama, Satoshi Ishibashi, Masahisa Inoue, Masufumi Takiguchi, Shinya Suzuki, Yoshinari Ohnishi
  • Journal Title: Life Science 84 Pages: 569-575
  • Peer Reviewed
• [Journal Article] Tissue-dependent preventive effect of metallothionein against DNA damage in dyslipidemic mice under repeated stresses of fasting or restraint (2009)
  • Author(s): Minoru Higashimoto, et.al.
  • Journal Title: Life Science 84 Pages: 569-575
  • Peer Reviewed
• [Journal Article] カドミウムの胎盤毒性-環境ホルモンを中心に (2008)
  • Author(s): 瀧口益史、吉原新一
  • Journal Title: 臨床検査 51 Pages: 1719-1723
• [Journal Article] カドミウムの胎盤毒性-環境ホルモン作用を中心に (2007)
  • Author(s): 瀧口益史ら
  • Journal Title: 臨床検査 Volume: 51 Pages: 1710-1723
• [Presentation] Effects of various metals on secretion of matrix metalloproteinase2 from mouse fibroblast cells (2010)
  • Author(s): Masufumi Takiguchi
  • Organizer: 49th Annual Meeting of Society of Toxicology
  • Place of Presentation: ソルトレイクシティーコンベンションセンター、米国
  • Year and Date: 2010-03-10
• [Presentation] Effects of various metals on secretion of matrix metalloproteinase2 from mouse fibroblast cells (2010)
  • Author(s): Masufumi Takiguchi, et.al.
  • Organizer: 49th Annual Meeting of Society of Toxicology
  • Place of Presentation: ソルトレイクシティー、米国
  • Year and Date: 2010-03-10
• [Presentation] ラットにおけるカドミウムの精巣毒性の系統差:金属トランスポーターの関与フォーラム (2009)
  • Author(s): 島田秀明
  • Organizer: 2009衛生薬学・環境トキシコロジー
  • Place of Presentation: 沖縄コンベンションセンター
  • Year and Date: 2009-11-05
• [Presentation] 種々の金属がメタロプロテイナーゼ活性及び細胞浸潤能に与える影響 (2008)
  • Author(s): 森石麻祐子
  • Organizer: 日本薬学会128年会
  • Place of Presentation: 横浜コンベンションセンター
  • Year and Date: 2008-03-27
• [Presentation] 種々の金属がメタロプロテイナーゼ活性及び細胞浸潤能に与える影響 (2008)
  • Author(s): 森石麻祐子ら
  • Organizer: 日本薬学会年会
  • Place of Presentation: 横浜
  • Year and Date: 2008-03-27
• [Presentation] メタロチオネインによるメタロプロテイナーゼ2(MMP2)発現への影響 (2007)
  • Author(s): 瀧口益史
  • Organizer: メタロチオネインおよびメタルバイオサイエンス研究会2007
  • Place of Presentation: 徳島文理大学
  • Year and Date: 2007-09-29