In Vitro Evaluation of No-Carrier-Added Radiolabeled Cisplatin ([<sup<189, 191</sup<Pt]cisplatin) Emitting Auger Electrons
Due to their short-range (2–500 nm), Auger electrons (Auger <i<e<sup<−</sup<</i<) have the potential to induce nano-scale physiochemical damage to biomolecules. Although DNA is the primary target of Auger <i<e</i<<sup<−</sup<, it remains challenging to...
Ausführliche Beschreibung
Autor*in: |
Honoka Obata [verfasserIn] Atsushi B. Tsuji [verfasserIn] Hitomi Sudo [verfasserIn] Aya Sugyo [verfasserIn] Katsuyuki Minegishi [verfasserIn] Kotaro Nagatsu [verfasserIn] Mikako Ogawa [verfasserIn] Ming-Rong Zhang [verfasserIn] |
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E-Artikel |
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Sprache: |
Englisch |
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2021 |
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Übergeordnetes Werk: |
In: International Journal of Molecular Sciences - MDPI AG, 2003, 22(2021), 9, p 4622 |
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Übergeordnetes Werk: |
volume:22 ; year:2021 ; number:9, p 4622 |
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Link aufrufen |
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DOI / URN: |
10.3390/ijms22094622 |
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Katalog-ID: |
DOAJ072613009 |
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10.3390/ijms22094622 doi (DE-627)DOAJ072613009 (DE-599)DOAJ8c82097bb9d84cd28fe97df478ad0168 DE-627 ger DE-627 rakwb eng QH301-705.5 QD1-999 Honoka Obata verfasserin aut In Vitro Evaluation of No-Carrier-Added Radiolabeled Cisplatin ([<sup<189, 191</sup<Pt]cisplatin) Emitting Auger Electrons 2021 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Due to their short-range (2–500 nm), Auger electrons (Auger <i<e<sup<−</sup<</i<) have the potential to induce nano-scale physiochemical damage to biomolecules. Although DNA is the primary target of Auger <i<e</i<<sup<−</sup<, it remains challenging to maximize the interaction between Auger <i<e</i<<sup<−</sup< and DNA. To assess the DNA-damaging effect of Auger <i<e</i<<sup<−</sup< released as close as possible to DNA without chemical damage, we radio-synthesized no-carrier-added (n.c.a.) [<sup<189, 191</sup<Pt]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 γH2AX 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 γH2AX foci was low (1%). Nevertheless, some cells treated with radio-cisplatin had γH2AX aggregates unlike non-radioactive cisplatin. These findings suggest n.c.a. radio-cisplatin binding to DNA causes severe DSBs by the release of Auger <i<e</i<<sup<−</sup< very close to DNA without chemical damage by carriers. Efficient radio-drug delivery to DNA is necessary for successful clinical application of Auger <i<e</i<<sup<−</sup<. Auger electron cisplatin <sup<191</sup<Pt <sup<189</sup<Pt radio-drug DNA double-strand break Biology (General) Chemistry Atsushi B. Tsuji verfasserin aut Hitomi Sudo verfasserin aut Aya Sugyo verfasserin aut Katsuyuki Minegishi verfasserin aut Kotaro Nagatsu verfasserin aut Mikako Ogawa verfasserin aut Ming-Rong Zhang verfasserin aut In International Journal of Molecular Sciences MDPI AG, 2003 22(2021), 9, p 4622 (DE-627)316340715 (DE-600)2019364-6 14220067 nnns volume:22 year:2021 number:9, p 4622 https://doi.org/10.3390/ijms22094622 kostenfrei https://doaj.org/article/8c82097bb9d84cd28fe97df478ad0168 kostenfrei https://www.mdpi.com/1422-0067/22/9/4622 kostenfrei https://doaj.org/toc/1661-6596 Journal toc kostenfrei https://doaj.org/toc/1422-0067 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 22 2021 9, p 4622 |
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10.3390/ijms22094622 doi (DE-627)DOAJ072613009 (DE-599)DOAJ8c82097bb9d84cd28fe97df478ad0168 DE-627 ger DE-627 rakwb eng QH301-705.5 QD1-999 Honoka Obata verfasserin aut In Vitro Evaluation of No-Carrier-Added Radiolabeled Cisplatin ([<sup<189, 191</sup<Pt]cisplatin) Emitting Auger Electrons 2021 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Due to their short-range (2–500 nm), Auger electrons (Auger <i<e<sup<−</sup<</i<) have the potential to induce nano-scale physiochemical damage to biomolecules. Although DNA is the primary target of Auger <i<e</i<<sup<−</sup<, it remains challenging to maximize the interaction between Auger <i<e</i<<sup<−</sup< and DNA. To assess the DNA-damaging effect of Auger <i<e</i<<sup<−</sup< released as close as possible to DNA without chemical damage, we radio-synthesized no-carrier-added (n.c.a.) [<sup<189, 191</sup<Pt]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 γH2AX 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 γH2AX foci was low (1%). Nevertheless, some cells treated with radio-cisplatin had γH2AX aggregates unlike non-radioactive cisplatin. These findings suggest n.c.a. radio-cisplatin binding to DNA causes severe DSBs by the release of Auger <i<e</i<<sup<−</sup< very close to DNA without chemical damage by carriers. Efficient radio-drug delivery to DNA is necessary for successful clinical application of Auger <i<e</i<<sup<−</sup<. Auger electron cisplatin <sup<191</sup<Pt <sup<189</sup<Pt radio-drug DNA double-strand break Biology (General) Chemistry Atsushi B. Tsuji verfasserin aut Hitomi Sudo verfasserin aut Aya Sugyo verfasserin aut Katsuyuki Minegishi verfasserin aut Kotaro Nagatsu verfasserin aut Mikako Ogawa verfasserin aut Ming-Rong Zhang verfasserin aut In International Journal of Molecular Sciences MDPI AG, 2003 22(2021), 9, p 4622 (DE-627)316340715 (DE-600)2019364-6 14220067 nnns volume:22 year:2021 number:9, p 4622 https://doi.org/10.3390/ijms22094622 kostenfrei https://doaj.org/article/8c82097bb9d84cd28fe97df478ad0168 kostenfrei https://www.mdpi.com/1422-0067/22/9/4622 kostenfrei https://doaj.org/toc/1661-6596 Journal toc kostenfrei https://doaj.org/toc/1422-0067 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 22 2021 9, p 4622 |
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10.3390/ijms22094622 doi (DE-627)DOAJ072613009 (DE-599)DOAJ8c82097bb9d84cd28fe97df478ad0168 DE-627 ger DE-627 rakwb eng QH301-705.5 QD1-999 Honoka Obata verfasserin aut In Vitro Evaluation of No-Carrier-Added Radiolabeled Cisplatin ([<sup<189, 191</sup<Pt]cisplatin) Emitting Auger Electrons 2021 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Due to their short-range (2–500 nm), Auger electrons (Auger <i<e<sup<−</sup<</i<) have the potential to induce nano-scale physiochemical damage to biomolecules. Although DNA is the primary target of Auger <i<e</i<<sup<−</sup<, it remains challenging to maximize the interaction between Auger <i<e</i<<sup<−</sup< and DNA. To assess the DNA-damaging effect of Auger <i<e</i<<sup<−</sup< released as close as possible to DNA without chemical damage, we radio-synthesized no-carrier-added (n.c.a.) [<sup<189, 191</sup<Pt]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 γH2AX 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 γH2AX foci was low (1%). Nevertheless, some cells treated with radio-cisplatin had γH2AX aggregates unlike non-radioactive cisplatin. These findings suggest n.c.a. radio-cisplatin binding to DNA causes severe DSBs by the release of Auger <i<e</i<<sup<−</sup< very close to DNA without chemical damage by carriers. Efficient radio-drug delivery to DNA is necessary for successful clinical application of Auger <i<e</i<<sup<−</sup<. Auger electron cisplatin <sup<191</sup<Pt <sup<189</sup<Pt radio-drug DNA double-strand break Biology (General) Chemistry Atsushi B. Tsuji verfasserin aut Hitomi Sudo verfasserin aut Aya Sugyo verfasserin aut Katsuyuki Minegishi verfasserin aut Kotaro Nagatsu verfasserin aut Mikako Ogawa verfasserin aut Ming-Rong Zhang verfasserin aut In International Journal of Molecular Sciences MDPI AG, 2003 22(2021), 9, p 4622 (DE-627)316340715 (DE-600)2019364-6 14220067 nnns volume:22 year:2021 number:9, p 4622 https://doi.org/10.3390/ijms22094622 kostenfrei https://doaj.org/article/8c82097bb9d84cd28fe97df478ad0168 kostenfrei https://www.mdpi.com/1422-0067/22/9/4622 kostenfrei https://doaj.org/toc/1661-6596 Journal toc kostenfrei https://doaj.org/toc/1422-0067 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 22 2021 9, p 4622 |
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10.3390/ijms22094622 doi (DE-627)DOAJ072613009 (DE-599)DOAJ8c82097bb9d84cd28fe97df478ad0168 DE-627 ger DE-627 rakwb eng QH301-705.5 QD1-999 Honoka Obata verfasserin aut In Vitro Evaluation of No-Carrier-Added Radiolabeled Cisplatin ([<sup<189, 191</sup<Pt]cisplatin) Emitting Auger Electrons 2021 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Due to their short-range (2–500 nm), Auger electrons (Auger <i<e<sup<−</sup<</i<) have the potential to induce nano-scale physiochemical damage to biomolecules. Although DNA is the primary target of Auger <i<e</i<<sup<−</sup<, it remains challenging to maximize the interaction between Auger <i<e</i<<sup<−</sup< and DNA. To assess the DNA-damaging effect of Auger <i<e</i<<sup<−</sup< released as close as possible to DNA without chemical damage, we radio-synthesized no-carrier-added (n.c.a.) [<sup<189, 191</sup<Pt]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 γH2AX 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 γH2AX foci was low (1%). Nevertheless, some cells treated with radio-cisplatin had γH2AX aggregates unlike non-radioactive cisplatin. These findings suggest n.c.a. radio-cisplatin binding to DNA causes severe DSBs by the release of Auger <i<e</i<<sup<−</sup< very close to DNA without chemical damage by carriers. Efficient radio-drug delivery to DNA is necessary for successful clinical application of Auger <i<e</i<<sup<−</sup<. Auger electron cisplatin <sup<191</sup<Pt <sup<189</sup<Pt radio-drug DNA double-strand break Biology (General) Chemistry Atsushi B. Tsuji verfasserin aut Hitomi Sudo verfasserin aut Aya Sugyo verfasserin aut Katsuyuki Minegishi verfasserin aut Kotaro Nagatsu verfasserin aut Mikako Ogawa verfasserin aut Ming-Rong Zhang verfasserin aut In International Journal of Molecular Sciences MDPI AG, 2003 22(2021), 9, p 4622 (DE-627)316340715 (DE-600)2019364-6 14220067 nnns volume:22 year:2021 number:9, p 4622 https://doi.org/10.3390/ijms22094622 kostenfrei https://doaj.org/article/8c82097bb9d84cd28fe97df478ad0168 kostenfrei https://www.mdpi.com/1422-0067/22/9/4622 kostenfrei https://doaj.org/toc/1661-6596 Journal toc kostenfrei https://doaj.org/toc/1422-0067 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 22 2021 9, p 4622 |
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Honoka Obata Atsushi B. Tsuji Hitomi Sudo Aya Sugyo Katsuyuki Minegishi Kotaro Nagatsu Mikako Ogawa Ming-Rong Zhang |
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in vitro evaluation of no-carrier-added radiolabeled cisplatin ([<sup<189, 191</sup<pt]cisplatin) emitting auger electrons |
callnumber |
QH301-705.5 |
title_auth |
In Vitro Evaluation of No-Carrier-Added Radiolabeled Cisplatin ([<sup<189, 191</sup<Pt]cisplatin) Emitting Auger Electrons |
abstract |
Due to their short-range (2–500 nm), Auger electrons (Auger <i<e<sup<−</sup<</i<) have the potential to induce nano-scale physiochemical damage to biomolecules. Although DNA is the primary target of Auger <i<e</i<<sup<−</sup<, it remains challenging to maximize the interaction between Auger <i<e</i<<sup<−</sup< and DNA. To assess the DNA-damaging effect of Auger <i<e</i<<sup<−</sup< released as close as possible to DNA without chemical damage, we radio-synthesized no-carrier-added (n.c.a.) [<sup<189, 191</sup<Pt]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 γH2AX 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 γH2AX foci was low (1%). Nevertheless, some cells treated with radio-cisplatin had γH2AX aggregates unlike non-radioactive cisplatin. These findings suggest n.c.a. radio-cisplatin binding to DNA causes severe DSBs by the release of Auger <i<e</i<<sup<−</sup< very close to DNA without chemical damage by carriers. Efficient radio-drug delivery to DNA is necessary for successful clinical application of Auger <i<e</i<<sup<−</sup<. |
abstractGer |
Due to their short-range (2–500 nm), Auger electrons (Auger <i<e<sup<−</sup<</i<) have the potential to induce nano-scale physiochemical damage to biomolecules. Although DNA is the primary target of Auger <i<e</i<<sup<−</sup<, it remains challenging to maximize the interaction between Auger <i<e</i<<sup<−</sup< and DNA. To assess the DNA-damaging effect of Auger <i<e</i<<sup<−</sup< released as close as possible to DNA without chemical damage, we radio-synthesized no-carrier-added (n.c.a.) [<sup<189, 191</sup<Pt]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 γH2AX 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 γH2AX foci was low (1%). Nevertheless, some cells treated with radio-cisplatin had γH2AX aggregates unlike non-radioactive cisplatin. These findings suggest n.c.a. radio-cisplatin binding to DNA causes severe DSBs by the release of Auger <i<e</i<<sup<−</sup< very close to DNA without chemical damage by carriers. Efficient radio-drug delivery to DNA is necessary for successful clinical application of Auger <i<e</i<<sup<−</sup<. |
abstract_unstemmed |
Due to their short-range (2–500 nm), Auger electrons (Auger <i<e<sup<−</sup<</i<) have the potential to induce nano-scale physiochemical damage to biomolecules. Although DNA is the primary target of Auger <i<e</i<<sup<−</sup<, it remains challenging to maximize the interaction between Auger <i<e</i<<sup<−</sup< and DNA. To assess the DNA-damaging effect of Auger <i<e</i<<sup<−</sup< released as close as possible to DNA without chemical damage, we radio-synthesized no-carrier-added (n.c.a.) [<sup<189, 191</sup<Pt]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 γH2AX 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 γH2AX foci was low (1%). Nevertheless, some cells treated with radio-cisplatin had γH2AX aggregates unlike non-radioactive cisplatin. These findings suggest n.c.a. radio-cisplatin binding to DNA causes severe DSBs by the release of Auger <i<e</i<<sup<−</sup< very close to DNA without chemical damage by carriers. Efficient radio-drug delivery to DNA is necessary for successful clinical application of Auger <i<e</i<<sup<−</sup<. |
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container_issue |
9, p 4622 |
title_short |
In Vitro Evaluation of No-Carrier-Added Radiolabeled Cisplatin ([<sup<189, 191</sup<Pt]cisplatin) Emitting Auger Electrons |
url |
https://doi.org/10.3390/ijms22094622 https://doaj.org/article/8c82097bb9d84cd28fe97df478ad0168 https://www.mdpi.com/1422-0067/22/9/4622 https://doaj.org/toc/1661-6596 https://doaj.org/toc/1422-0067 |
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