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Effect of poly(ADP-ribosyl)ation inhibitors on the genotoxic effects of the boron neutron capture reaction

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dc.contributor.authorOliveira, NG
dc.contributor.authorCastro, M
dc.contributor.authorRodrigues, AS
dc.contributor.authorGoncalves, IC
dc.contributor.authorMartins, C
dc.contributor.authorRico, JMT
dc.contributor.authorRueff, J
dc.date.accessioned2015-12-30T10:18:14Z
dc.date.available2015-12-30T10:18:14Z
dc.date.issued2005
dc.description.abstractThe boron neutron capture (BNC) reaction results from the interaction of B-10 with low-energy thermal neutrons and gives rise to highly damaging lithium and alpha-particles. In this work the genotoxicity caused by the BNC reaction in V79 Chinese hamster cells was evaluated in the presence of poly(ADP-ribosyl)ation inhibitors. Poly(ADP-ribose) polymerase-1 (PARP-1), the most important member of the PARP enzyme family, is considered to be a constitutive factor of the DNA damage surveillance network present in eukaryotic cells, acting through a DNA break sensor function. Inhibition of poly(ADP-ribosyl)ation was achieved with the classical compound 3-aminobenzamide (3-AB), and with two novel and very potent inhibitors, 5-aminoisoquinolinone (5-AIQ) and PJ-34. Dose-response increases in the frequencies of aberrant cells excluding gaps (%ACEG) and chromosomal aberrations excluding gaps per cell (CAEG/cell) were observed for increasing exposures to the BNC reaction. The presence of 3-AB did not increase the %ACEG or CAEG/cell, nor did it change the pattern of the induced chromosomal aberrations. Results with 5-AIQ and PJ-34 were in agreement with the results obtained with 3-AB. We further studied the combined effect of a PARP inhibitor and a DNA-dependent protein kinase (DNA-PK) inhibitors (3-AB and wortmannin, respectively) on the genotoxicity of the BNC reaction, by use of the cytokinesis-block micronucleus assay. DNA-PK is also activated by DNA breaks and binds DNA ends, playing a role of utmost importance in the repair of double-strand breaks. Our results show that the inhibition of poly(ADP-ribosyl)ation does not particularly modify the genotoxicity of the BNC reaction, and that PARP inhibition together with a concomitant inhibition of DNA-PK revealed barely the same sensitizing effect as DNA-PK inhibition per se. (c) 2005 Published by Elsevier B.V.
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dc.identifier.citationMUTATION RESEARCH-GENETIC TOXICOLOGY AND ENVIRONMENTAL MUTAGENESIS. - Vol. 583, n. 1 (MAY 2 2005), p. 36-48
dc.identifier.doihttp://dx.doi.org/10.1016/j.mrgentox.2005.01.015
dc.identifier.issn1383-5718
dc.identifier.urihttp://hdl.handle.net/10451/21483
dc.language.isoeng
dc.publisherELSEVIER SCIENCE BV
dc.subjectBiotechnology & Applied Microbiology
dc.subjectGenetics & Heredity
dc.subjectToxicology
dc.titleEffect of poly(ADP-ribosyl)ation inhibitors on the genotoxic effects of the boron neutron capture reaction
dc.typejournal article
dspace.entity.typePublication
oaire.citation.endPage48por
oaire.citation.startPage36por
oaire.citation.titleMUTATION RESEARCH-GENETIC TOXICOLOGY AND ENVIRONMENTAL MUTAGENESISpor
oaire.citation.volumeVol. 583por
rcaap.rightsrestrictedAccess
rcaap.typearticle

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