About: Analysis of covalent ellipticine- and doxorubicin-derived adducts in DNA of neuroblastoma cells by the P-32-postlabeling technique     Goto   Sponge   NotDistinct   Permalink

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  • Ellipticine and doxorubicin are antineoplastic agents, whose action is based mainly on DNA damage such as intercalation, inhibition of topoisomerase II and formation of covalent DNA adducts. The key target to resolve which of these mechanisms are responsible for ellipticine and doxorubicin anticancer effects is the development of suitable methods for identifying their individual DNA-damaging effects. Here, the P-32-postlabeling method was tested to detect covalent DNA adducts formed by ellipticine and doxorubicin. Results. Two covalent ellipticine-derived DNA adducts, which are associated with cytotoxicity of ellipticine to human UKF-NB-3 and UKF-NB-4 neuroblastoma cell lines, were detected by the P-32-postlabeling method. These adducts are identical to those formed by the ellipticine metabolites, 13-hydroxy- and 12-hydroxyellipticine. In contrast, no covalent adducts formed by doxorubicin in DNA of these neuroblastoma cells and in DNA incubated with this drug and formaldehyde in vitro were detectable by the P-32-postlabeling assay. Conclusions. The results presented in this paper are the first to demonstrate that in contrast to covalent DNA adducts formed by ellipticine, the adducts generated by formaldehyde-mediated covalent binding of doxorubicin to DNA are not detectable by the P-32-postlabeling assay. No DNA adducts were, detectable either in vitro, in incubations of DNA with doxorubicin or in DNA of neuroblastoma cells treated with this drug. The results also suggest that covalent binding of ellipticine to DNA of UKF-NB-3 and UKF-NB-4 neuroblastoma cell lines is the predominant mechanism responsible for the cytotoxicity of this drug. To understand the mechanisms of doxorubicin anticancer effects on neuroblastoma cells, development of novel methods for identifying covalent doxorubicin-derived DNA adducts is the major challenge for further research.
  • Ellipticine and doxorubicin are antineoplastic agents, whose action is based mainly on DNA damage such as intercalation, inhibition of topoisomerase II and formation of covalent DNA adducts. The key target to resolve which of these mechanisms are responsible for ellipticine and doxorubicin anticancer effects is the development of suitable methods for identifying their individual DNA-damaging effects. Here, the P-32-postlabeling method was tested to detect covalent DNA adducts formed by ellipticine and doxorubicin. Results. Two covalent ellipticine-derived DNA adducts, which are associated with cytotoxicity of ellipticine to human UKF-NB-3 and UKF-NB-4 neuroblastoma cell lines, were detected by the P-32-postlabeling method. These adducts are identical to those formed by the ellipticine metabolites, 13-hydroxy- and 12-hydroxyellipticine. In contrast, no covalent adducts formed by doxorubicin in DNA of these neuroblastoma cells and in DNA incubated with this drug and formaldehyde in vitro were detectable by the P-32-postlabeling assay. Conclusions. The results presented in this paper are the first to demonstrate that in contrast to covalent DNA adducts formed by ellipticine, the adducts generated by formaldehyde-mediated covalent binding of doxorubicin to DNA are not detectable by the P-32-postlabeling assay. No DNA adducts were, detectable either in vitro, in incubations of DNA with doxorubicin or in DNA of neuroblastoma cells treated with this drug. The results also suggest that covalent binding of ellipticine to DNA of UKF-NB-3 and UKF-NB-4 neuroblastoma cell lines is the predominant mechanism responsible for the cytotoxicity of this drug. To understand the mechanisms of doxorubicin anticancer effects on neuroblastoma cells, development of novel methods for identifying covalent doxorubicin-derived DNA adducts is the major challenge for further research. (en)
Title
  • Analysis of covalent ellipticine- and doxorubicin-derived adducts in DNA of neuroblastoma cells by the P-32-postlabeling technique
  • Analysis of covalent ellipticine- and doxorubicin-derived adducts in DNA of neuroblastoma cells by the P-32-postlabeling technique (en)
skos:prefLabel
  • Analysis of covalent ellipticine- and doxorubicin-derived adducts in DNA of neuroblastoma cells by the P-32-postlabeling technique
  • Analysis of covalent ellipticine- and doxorubicin-derived adducts in DNA of neuroblastoma cells by the P-32-postlabeling technique (en)
skos:notation
  • RIV/00216208:11310/12:10126293!RIV13-GA0-11310___
http://linked.open...avai/predkladatel
http://linked.open...avai/riv/aktivita
http://linked.open...avai/riv/aktivity
  • I, P(ED1.1.00/02.0068), P(GAP301/10/0356)
http://linked.open...iv/cisloPeriodika
  • 2
http://linked.open...vai/riv/dodaniDat
http://linked.open...aciTvurceVysledku
http://linked.open.../riv/druhVysledku
http://linked.open...iv/duvernostUdaju
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  • 122097
http://linked.open...ai/riv/idVysledku
  • RIV/00216208:11310/12:10126293
http://linked.open...riv/jazykVysledku
http://linked.open.../riv/klicovaSlova
  • cancer; P-32-postlabeling; DNA adducts; neuroblastoma; doxorubicin; ellipticine (en)
http://linked.open.../riv/klicoveSlovo
http://linked.open...odStatuVydavatele
  • CZ - Česká republika
http://linked.open...ontrolniKodProRIV
  • [F8E8245C5BD9]
http://linked.open...i/riv/nazevZdroje
  • Biomedical papers of the Medical Faculty of the University Palacky, Olomouc, CzechoSK
http://linked.open...in/vavai/riv/obor
http://linked.open...ichTvurcuVysledku
http://linked.open...cetTvurcuVysledku
http://linked.open...vavai/riv/projekt
http://linked.open...UplatneniVysledku
http://linked.open...v/svazekPeriodika
  • 156
http://linked.open...iv/tvurceVysledku
  • Eckschlager, Tomáš
  • Frei, Eva
  • Kizek, René
  • Poljaková, Jitka
  • Stiborová, Marie
http://linked.open...ain/vavai/riv/wos
  • 000306401700005
issn
  • 1213-8118
number of pages
http://bibframe.org/vocab/doi
  • 10.5507/bp.2012.043
http://localhost/t...ganizacniJednotka
  • 11310
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