Development of a single DNA adduct-caused gene mutation assay as a model of low-dose exposure

2012 Fiscal Year Final Research Report

• Project/Area Number: 22710068
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Risk sciences of radiation/Chemicals
• Research Institution: National Institute of Health Sciences
• Principal Investigator: YASUI Manabu 国立医薬品食品衛生研究所, 変異遺伝部, 主任研究員 (50435707)
• Project Period (FY): 2010 – 2012
• Keywords: トキシコロジー / DNA 付加体 / 閾値 / 放射線 / 遺伝毒性発がん物質 / 環境

Research Abstract

Conventional technique of investigating an influence of low-dose exposure, commonly extrapolated from high-dose to low-dose region in Toxicology, is limited. Then, we have developed a new experimental system as a model of low-dose exposure, which can be used to determine the mutagenicity of synthetic DNA adducts at exon5 of thymidine kinase gene in human lymphoblastoid TSCER122 cells, derived from TK6 cell line. As a result, when an adduct forms at least one molecule on genomic DNA, it can cause gene mutation. The observation supports the idea that genotoxic carcinogens have no thresholds for the cancer risk. However, DNA repair functions in this experimental system do not work properly. In order to confirm the existence of threshold, it is necessary to study in detail the mechanisms of a single DNA adduct-caused gene mutation using TSCER122 cells knocked out DNA repair genes.

Research Products

• [Journal Article] Miscoding properties of 8-chloro-2'-deoxyguanosine, a hypochlorous acid-induced DNA adduct,catalysed by human DNA polymerases (2013)
  • Author(s): Sassa A, Kamoshita N, Matsuda T, Ishii Y,Kuraoka I, Nohmi T, Ohta T, Honma M, and Yasui M
  • Journal Title: Mutagenesis Volume: 28 Pages: 81-88
• [Journal Article] Induction of TK mutations in human lymphoblastoid TK6 cells by the rat carcinogen 3-chloro-4-(dichloromethyl)-5-hydro xy-2(5H)-furanone (MX) (2011)
  • Author(s): Hakulinen P, Yamamoto A, Koyama N, Kumita W, Yasui M, and Honma M
  • Journal Title: Mutation Res Volume: 725 Pages: 43-49
  • DOI: DOI:10.1016/j.mrgentox.2011.07.004
• [Journal Article] Phenylalanine 171 is a molecular brake for translesion synthesis across benzo[a]pyrene-guanine adducts by human DNA polymerase kappa (2011)
  • Author(s): Sassa A, Niimi N, Fujimoto H, Katafuchi A, Gruz P, Yasui M, Gupta RC, Johnson F, Ohta T, and Nohmi T
  • Journal Title: Mutation Res. Volume: 718 Pages: 10-17
  • DOI: DOI:10.1016/j.mrgentox.2010.11.002
• [Journal Article] Acrylamide genotoxicity in young versus adult gpt delta male rats (2011)
  • Author(s): Koyama N, Yasui M, Kimura A, Takami S, Suzuki T, Masumura K, Nohmi T, Masuda S, Kinae N, Matsuda T, Imai T, and Honma M
  • Journal Title: Mutagenesis Volume: 26 Pages: 545-549
  • DOI: DOI:10.1093/mutage/ger014
• [Journal Article] Mutational specificities of brominated DNA adducts catalyzed by human DNA polymerases (2011)
  • Author(s): Sassa A, Ohta T, Nohmi T, Honma M, and Yasui M
  • Journal Title: J. Mol. Biol. Volume: 406 Pages: 679-686
  • DOI: DOI:10.1016/j.jmb.2011.01.005.
• [Journal Article] Live cell imaging of micronucleus formation and development (2010)
  • Author(s): Yasui M, Koyama N, Koizumi T, Senda-Murata K, Takashima Y, Hayashi M, Sugimoto K, and Honma M
  • Journal Title: Mutation Res. Volume: 692 Pages: 12-18
  • DOI: DOI:10.1016/j.mrfmmm.2010.07.009.
• [Presentation] Mutation analysis of site-specific brominated DNA adducts located in the genome of human lymphoblastoid cells (2013)
  • Author(s): Yasui M, Kanemaru Y, Kamoshita N, Sassa A, and Honma M
  • Organizer: Mammalian DNA Repair in Gordon Research Conferences
  • Place of Presentation: Ventura, USA
  • Year and Date: 20130200
• [Presentation] 極低線量暴露を想定した新しいDNA 付加体1分子による遺伝子変異解析系の基礎的研究 (2012)
  • Author(s): 安井学,鴨下渚,本間正充
  • Organizer: 日本放射線影響学会第55回大会
  • Place of Presentation: 仙台市
  • Year and Date: 20120900
• [Presentation] ゲノムの特定部位に導入させたブロモ化DNA 付加体の突然変異誘発能の解析 (2012)
  • Author(s): 兼丸祐紀,鴨下渚,佐々彰,本間正充,安井学
  • Organizer: 日本環境変異原学会第41回大会
  • Place of Presentation: 静岡市
  • Year and Date: 20120100
• [Presentation] ゲノムDNAに導入した1 分子のDNA 付加体の運命 (2011)
  • Author(s): 安井学,鴨下渚,本間正充
  • Organizer: 第34回日本分子生物学会年会
  • Place of Presentation: 横浜市
  • Year and Date: 20111200
• [Presentation] 8-クロログアニンDNA 付加体を含むオリゴマーの構築とその誤塩基対形成機構に関する研究 (2011)
  • Author(s): 安井学,佐々彰,鴨下渚,松田知成,太田敏博,能美健彦,本間正充
  • Organizer: 日本環境変異原学会第40回大会
  • Place of Presentation: 東京都
  • Year and Date: 20111100
• [Presentation] gpt delta トランスジェニックラットを用いたライフステージ(週齢)を考慮したアクリルアミドの遺伝毒性評価 (2011)
  • Author(s): 小山直己,安井学,木村葵,高見成昭, 鈴木拓也,増村健一,能美健彦,増田修 一,木苗直秀,松田知成,今井俊夫,本 間正充
  • Organizer: 第38回日本トキシコロジー学会学術年会
  • Place of Presentation: 横浜市
  • Year and Date: 20110700
• [Presentation] Miscoding properties of brominated DNA adducts catalyzed by human DNA polymerases (2011)
  • Author(s): Yasui M, Sassa A, Ohta T, Nohmi T, and Honma M
  • Organizer: UKEMS / Dutch EMS-sponsored Workshop on Biomarker of Exposure and Oxidative DNA Damage
  • Place of Presentation: ミュンスター,ドイツ
  • Year and Date: 20110300
• [Presentation] Miscoding events during DNA synthesis past brominated DNA adducts (2010)
  • Author(s): Sassa A, Ohta T, Nohmi T, Honma M, and Yasui M
  • Organizer: The 2nd Asian Conference of Environmental Mutagen
  • Place of Presentation: パタヤ,タイ
  • Year and Date: 20101200
• [Presentation] DNA2 本鎖切断修復に対する低線量放射線等の環境ストレスの影響 (2010)
  • Author(s): 本間正充,安井学,堀端克良,鈴木哲矢,谷田貝文夫
  • Organizer: 第33回日本分子生物学会年会・第83 回 日本生化学会大会 合同大会
  • Place of Presentation: 横浜市
  • Year and Date: 20101200
• [Presentation] 臭素化DNA 付加体の誤塩基対形成機構 (2010)
  • Author(s): 佐々彰, 太田敏博, 能美健彦, 本間正 充, 安井学
  • Organizer: 日本環境変異原学会第39回大会
  • Place of Presentation: つくば市
  • Year and Date: 20101100
• [Presentation] DNA 付加体を含む修飾DNA オリゴマーの生化学的構築法の最適化 (2010)
  • Author(s): 安井学, 佐々彰, 鴨下渚, 太田敏博, 松田知成, 能美健彦, 本間正充
  • Organizer: 日本環境変異原学会第39回大会
  • Place of Presentation: つくば市
  • Year and Date: 20101100
• [Remarks]
  • URL: http://www.nihs.go.jp/dgm/