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Although DNA is the primary target of\nAuger e????, it remains challenging to maximize the interaction between Auger e???? and DNA. To assess\nthe DNA-damaging effect of Auger e???? released as close as possible to DNA without chemical damage,\nwe radio-synthesized no-carrier-added (n.c.a.) [189, 191Pt]cisplatin and evaluated both its in vitro\nproperties and DNA-damaging effect. Cellular uptake, intracellular distribution, and DNA binding\nwere investigated, and DNA double-strand breaks (DSBs) were evaluated by immunofluorescence\nstaining of \nH2AX and gel electrophoresis of plasmid DNA. Approximately 20% of intracellular radio-\nPt was in a nucleus, and about 2% of intra-nucleus radio-Pt bound to DNA, although uptake of n.c.a.\nradio-cisplatin was low (0.6% incubated dose after 25-h incubation), resulting in the frequency of cells\nwith \nH2AX foci was low (1%). Nevertheless, some cells treated with radio-cisplatin had \nH2AX\naggregates unlike non-radioactive cisplatin. These findings suggest n.c.a. radio-cisplatin binding to\nDNA causes severe DSBs by the release of Auger e???? very close to DNA without chemical damage\nby carriers. 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In Vitro Evaluation of No-Carrier-Added Radiolabeled Cisplatin ([189, 191Pt]cisplatin) Emitting Auger Electrons
https://repo.qst.go.jp/records/82791
https://repo.qst.go.jp/records/827913e30313a-08d2-4baf-a05f-5ae0ce5187fa
Item type | 学術雑誌論文 / Journal Article(1) | |||||
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公開日 | 2021-05-06 | |||||
タイトル | ||||||
タイトル | In Vitro Evaluation of No-Carrier-Added Radiolabeled Cisplatin ([189, 191Pt]cisplatin) Emitting Auger Electrons | |||||
言語 | ||||||
言語 | eng | |||||
資源タイプ | ||||||
資源タイプ識別子 | http://purl.org/coar/resource_type/c_6501 | |||||
資源タイプ | journal article | |||||
アクセス権 | ||||||
アクセス権 | metadata only access | |||||
アクセス権URI | http://purl.org/coar/access_right/c_14cb | |||||
著者 |
Honoka, Obata
× Honoka, Obata× Atsushi, Tsuji× Hitomi, Sudo× Aya, Sugyo× Katsuyuki, Minegishi× Kotaro, Nagatsu× Mikako, Ogawa× Zhang, Ming-Rong× Honoka, Obata× Atsushi, Tsuji× Hitomi, Sudo× Aya, Sugyo× Katsuyuki, Minegishi× Kotaro, Nagatsu× Mikako, Ogawa× Zhang, Ming-Rong |
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抄録 | ||||||
内容記述タイプ | Abstract | |||||
内容記述 | Due to their short-range (2–500 nm), Auger electrons (Auger e????) have the potential to induce nano-scale physiochemical damage to biomolecules. Although DNA is the primary target of Auger e????, it remains challenging to maximize the interaction between Auger e???? and DNA. To assess the DNA-damaging effect of Auger e???? released as close as possible to DNA without chemical damage, we radio-synthesized no-carrier-added (n.c.a.) [189, 191Pt]cisplatin and evaluated both its in vitro properties and DNA-damaging effect. Cellular uptake, intracellular distribution, and DNA binding were investigated, and DNA double-strand breaks (DSBs) were evaluated by immunofluorescence staining of H2AX and gel electrophoresis of plasmid DNA. Approximately 20% of intracellular radio- Pt was in a nucleus, and about 2% of intra-nucleus radio-Pt bound to DNA, although uptake of n.c.a. radio-cisplatin was low (0.6% incubated dose after 25-h incubation), resulting in the frequency of cells with H2AX foci was low (1%). Nevertheless, some cells treated with radio-cisplatin had H2AX aggregates unlike non-radioactive cisplatin. These findings suggest n.c.a. radio-cisplatin binding to DNA causes severe DSBs by the release of Auger e???? very close to DNA without chemical damage by carriers. Efficient radio-drug delivery to DNA is necessary for successful clinical application of Auger e????. Keywords: Auger electron; cisplatin; 191Pt; 189Pt; radio-drug; DNA double-strand break; H2AX |
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書誌情報 |
International Journal of Molecular Sciences 巻 22, 号 9, p. 4622, 発行日 2021-05 |
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出版者 | ||||||
出版者 | MDPI | |||||
ISSN | ||||||
収録物識別子タイプ | ISSN | |||||
収録物識別子 | 1422-0067 | |||||
DOI | ||||||
識別子タイプ | DOI | |||||
関連識別子 | 10.3390/ijms22094622 | |||||
関連サイト | ||||||
識別子タイプ | URI | |||||
関連識別子 | https://www.mdpi.com/1422-0067/22/9/4622 |