Mutagenic risk assesment of Anti-Malarial Drugs to Plasmodium Genome and Mechanisms to induce Mutations
| Project/Area Number |
26670205
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| Research Category |
Grant-in-Aid for Challenging Exploratory Research
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| Allocation Type | Multi-year Fund |
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| Research Field |
Parasitology (including sanitary zoology)
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| Research Institution | National Center for Global Health and Medicine |
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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)
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| 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)
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| Project Period (FY) |
2014-04-01 – 2016-03-31
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| Project Status |
Completed (Fiscal Year 2015)
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| 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)
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| 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 |
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| 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.
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Report
(3 results)
Research Products
(2 results)
