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Titolo:
DNA cleavage by In-111-labeled oligodeoxyribonucleotide
Autore:
Karamychev, VN; Panyutin, IG; Kim, MK; Le, N; Paik, CH; Carrasquillo, JA; Reed, MW; Neumann, RD;
Indirizzi:
NIH, Warren G Magnuson Clin Ctr, Dept Nucl Med, Bethesda, MD 20892 USA NIH Bethesda MD USA 20892 Clin Ctr, Dept Nucl Med, Bethesda, MD 20892 USA Epoch Pharmaceut Inc, Bothell, WA USA Epoch Pharmaceut Inc Bothell WA USA poch Pharmaceut Inc, Bothell, WA USA Novosibirsk Bioorgan Chem Inst, Novosibirsk 630090, Russia Novosibirsk Bioorgan Chem Inst Novosibirsk Russia 630090 630090, Russia
Titolo Testata:
JOURNAL OF NUCLEAR MEDICINE
fascicolo: 6, volume: 41, anno: 2000,
pagine: 1093 - 1101
SICI:
0161-5505(200006)41:6<1093:DCBIO>2.0.ZU;2-G
Fonte:
ISI
Lingua:
ENG
Soggetto:
TRIPLEX-FORMING-OLIGONUCLEOTIDES; I-125 LABELED OLIGONUCLEOTIDES; DECAY; DAMAGE; OLIGODEOXYNUCLEOTIDES; MODEL; I125;
Keywords:
Auger electrons; In-111; DNA double-strand breaks;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Life Sciences
Citazioni:
32
Recensione:
Indirizzi per estratti:
Citazione:
V.N. Karamychev et al., "DNA cleavage by In-111-labeled oligodeoxyribonucleotide", J NUCL MED, 41(6), 2000, pp. 1093-1101

Abstract

We studied the fine structure of DNA damage produced by the decay of In-111 incorporated into duplex and tripler DNA strands to evaluate the usefulness of this radionuclide for sequence-specific DNA cleavage. Methods: Oligodeoxyribonucleotides (ODNs) were prepared with In-111 attached by diethylenetriaminepentaacetic acid (DTPA) at the 5' end or 3' end through a long chemical linker or to an internal nucleotide position through a short linker. Subsequent formation of DNA duplexes and triplexes was confirmed by gel electrophoresis. The In-111-induced breaks were assayed in denaturing polyacrylamide gel electrophoresis with a single-nucleotide resolution. Results: In-111-labeled oligonucleotides of high specific activity (740-1554 TBq/mmol) were synthesized. The presence of the bulky In-111-DTPA group did not impede duplex or tripler formation. Localized DNA breaks were observed in all duplexes and triplexes formed. The majority of DNA breaks in duplex formations were located within +/-10 nucleotides from the site of attachment of the In-111-bearing linker. The yield of DNA breaks per decay was 0.38 in a duplex with internally modified ODNs. This is nearly 2 times less than the yield of DNA breaks in the same duplex with I-125 attached through the same linker. The yield of DNA breaks in the pyrimidine and purine strands of DNA triplexes with In-111 attached to the tripler-forming ODNs through the linkers of different length varied from 0.05 to 0.10. The distribution of DNA breaks was wider in comparison with the duplex experiment. The lower yields ofbreaks per In-111 decay compared with I-125 may be not only the result of lower deposited energy but also of the ionic repulsion of the negatively charged In-111-DTPA group from the DNA strands. Conclusion: We have shown that decay of In-111 produces highly localized DNA breaks. In-111 introduced into triplex- and duplex-forming ODNs through hydrocarbon linkers produces sequence-specific DNA strand breaks with an efficiency nearly comparable with that of I-125. These findings are supportive of our proposed use of In-111-ODNs for gene-specific radiotherapy.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 26/09/20 alle ore 08:28:50