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Mutagenic risk assesment of Anti-Malarial Drugs to Plasmodium Genome and Mechanisms to induce Mutations

Research Project

Project/Area Number 26670205
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeMulti-year Fund
Research Field Parasitology (including sanitary zoology)
Research InstitutionNational Center for Global Health and Medicine

Principal Investigator

KANO Shungo  国立研究開発法人国立国際医療研究センター, その他部局等, 研究員 (50648409)

Co-Investigator(Kenkyū-buntansha) KOMAKI Kanako (YASUDA Kanako)  国立国際医療研究センター研究所, 室長 (50415551)
Project Period (FY) 2014-04-01 – 2016-03-31
Project Status Completed (Fiscal Year 2015)
Budget Amount *help
¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2014: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Keywords突然変異 / 抗マラリア薬 / 変異原性 / シャトルベクター / コメットアッセイ / マラリア / 突然変異スペクトル / マラリア原虫
Outline of Final Research Achievements

To prove the working hypothesis that antimalarial drugs could be mutagenic to the parasite Plasmodium falciparum, a shuttle vector system was established, by which neutral mutations in the parasites in vivo that carry the shuttle vector containing the mutation reporter gene rpsL are screened using the conventional bacterial system in the presence of streptomycin. This system indeed detected different mutation spectra between control groups and ones exposed either to the chemical mutagen ENU or to the anti-malarial drug chloroquine (CQ). However, it emerged that this system alone was inconvenient for accurately estimating the true mutation frequencies since it was difficult to distinguish mutations occurring in the parasites from those in the bacteria, in which unclear mutations are randomly induced. To compensate for this low reliability, a comet assay was also applied, which was helpful in narrowing down the range of concentrations of CQ to be investigated.

Report

(3 results)
  • 2015 Annual Research Report   Final Research Report ( PDF )
  • 2014 Research-status Report
  • Research Products

    (2 results)

All 2015

All Presentation (2 results) (of which Int'l Joint Research: 1 results)

  • [Presentation] A NEW SHUTTLE VECTOR SYSTEM TO EVALUATE POTENTIAL MUTAGENIC RISKS OF ANTI-MALARIAL DRUGS2015

    • Author(s)
      Shungo KANO, Shigeyuki KANO, Kanako Komaki-Yasuda
    • Organizer
      25th Annual Molecular Parasitology/Vector Biology Symposium
    • Place of Presentation
      Athens, Georgia, USA
    • Year and Date
      2015-04-28 – 2015-04-29
    • Related Report
      2014 Research-status Report
  • [Presentation] A New Shuttle Vector System To Evaluate Potential Mutagenic Risks Of Anti-Malarial Drugs.2015

    • Author(s)
      Shungo Kano, Shigeyuki Kano, and Kanako Komaki-Yasuda
    • Organizer
      the 25th Annual Molecular Parasitology Vector Biology Symposium
    • Place of Presentation
      Athens, Georgia, USA
    • Year and Date
      2015-04-28
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research

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Published: 2014-04-04   Modified: 2017-05-10  

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