Publicação
Poly (ADP-ribose) polymerase-1 deficiency does not affect ethylnitrosourea mutagenicity in liver and testis of lacZ transgenic mice
| dc.contributor.author | Louro, Henriqueta | |
| dc.contributor.author | Faustino, Inês | |
| dc.contributor.author | Dias, Anabela | |
| dc.contributor.author | Boavida, Maria G. | |
| dc.date.accessioned | 2011-09-08T13:37:58Z | |
| dc.date.available | 2011-09-08T13:37:58Z | |
| dc.date.issued | 2010-05 | |
| dc.description.abstract | Poly (ADP-ribose) polymerase-1 (Parp1) has been implicated in DNA base excision repair, single- and double-strand break repair pathways, as well as in cell death by apoptosis or necrosis. We used Parp1(-/-) lacZ plasmid-based transgenic mice to investigate whether Parp1 deficiency influences the in vivo mutagenic and clastogenic response to the alkylating agent N-ethyl-N-Nitrosourea (ENU) in somatic and germ-cell tissues. The comparison of the lacZ mutant frequencies (MFs) between Parp1(+/+) and Parp1(-/-) mice showed that the ablation of Parp1 does not affect the spontaneous or ENU-induced MFs in liver and testis. In addition, the spectrum of the ENU-induced mutations was not dependent on the Parp1 status, given that similar spectra, consisting mostly of point mutations and a small fraction of deletions/insertions, wereobserved in organs of both Parp1(-/-) and Parp1(+/+) mice. Sequencing of point mutations revealed a consistent significant increase in A:T --> T:A base substitutions, typically induced by ENU. Overall, we observed that neither the frequency nor the spectrum of ENU-induced mutations demonstrated a specificity that could be attributed to the Parp1 impairment in mice organs. The analysis of micronucleus frequency in peripheral blood reticulocytes showed that ENU was clastogenic in both Parp1(-/-) and Parp1(+/+) mice and had a strong cytotoxic effect in Parp1(-/-) mice only. The present data suggest that, at a whole-organism level, Parp1-independent repair mechanisms may be operative in the removal of ENU-induced DNA lesions or that highly damaged cells may be preferentially committed to death when Parp1 is inactivated. | por |
| dc.identifier.citation | Environ Mol Mutagen. 2010 May;51(4):322-9. Epub 2010 Mar 1 | por |
| dc.identifier.issn | 0893-6692 | |
| dc.identifier.uri | http://hdl.handle.net/10400.18/131 | |
| dc.language.iso | eng | por |
| dc.peerreviewed | yes | por |
| dc.publisher | Wiley | por |
| dc.relation.publisherversion | http://onlinelibrary.wiley.com/doi/10.1002/em.20555/pdf | por |
| dc.subject | Parp1 | por |
| dc.subject | LacZ mice | por |
| dc.subject | ENU | por |
| dc.subject | Mutant frequency | por |
| dc.subject | mutation spectrum | por |
| dc.subject | Doenças Genéticas | por |
| dc.title | Poly (ADP-ribose) polymerase-1 deficiency does not affect ethylnitrosourea mutagenicity in liver and testis of lacZ transgenic mice | por |
| dc.type | journal article | |
| dspace.entity.type | Publication | |
| oaire.citation.endPage | 329 | por |
| oaire.citation.startPage | 322 | por |
| oaire.citation.title | Environmental and Molecular Mutagenesis | por |
| rcaap.rights | restrictedAccess | por |
| rcaap.type | article | por |