English   español  
Por favor, use este identificador para citar o enlazar a este item: http://hdl.handle.net/10261/169551
COMPARTIR / IMPACTO:
Estadísticas
logo share SHARE   Add this article to your Mendeley library MendeleyBASE
Visualizar otros formatos: MARC | Dublin Core | RDF | ORE | MODS | METS | DIDL
Exportar a otros formatos:

Título

Analysis of genetic and phenotypic interactions between DNA damage / genotoxicity pathways in heart tissue and heart damage caused by anthracyclines and taxanes

AutorCorchado Cobos, Roberto; Gómez-Vecino, Aurora; García-Macías, Carmen; Rodrigues Teixeira, Telmo; Isidoro-García, María; García Sánchez, Asunción; Galvis-Jiménez, Julie Milena; Ramos, Isabel ; Blanco-Gómez, Adrián ; Sánchez-Fernández, Pedro Luis; Pérez-Losada, J.
Fecha de publicación2016
EditorSociedad Española de Bioquímica y Biología Molecular
CitaciónXXXIX Congreso de la SEBBM (2016)
Resumen[Introduction]: Anthracyclines are among the most widely used chemotherapeutic agents in the treatment of a variety of tumors. The identification of genetic and molecular factors responsible for the increased risk of CDA (cardiotoxicity due to anthracyclines) will contribute to a better understanding of their pathophysiology, which could lead to new approaches to predict, prevent and treat this serious complication of chemotherapy. [Working hypothesis]: Based on two premises: (i) anthracyclines have a pro-genotoxicity effect. Differences in anti-genotoxicity pathways and genetic variants could contribute to different susceptibility to CDA. (ii) The usefulness of a simplified model system to identify genetic determinants involved in the quantitative inheritance of complex traits. [Materials and methods]: We treated a cohort of mice carrying ERBB2 breast cancer with doxorubicin alone (N = 85) or in combination with docetaxel (N = 77). The cohort was generated by a backcross between two genetically homogeneous strains, C57BL/6 and FVB, with the latter carrying the MMTV- ErbB2 / Neu transgene. Histopathologic heart damage was assessed by quantification of histologic parameters using Ariol automated system. Cardiac level of some key anti-genotoxicity proteins: ATR total, pp53 (Ser15), P21 Total, Total MDM2, pHistone H2AX (Ser139), pCHK1 (Ser345) and pCHK2 (Thr68) were quantified. [Results]: We identified: (i) differences dependent on the genetic background in both cardiotoxicity and the levels of proteins implicated in the pathways protecting against genotoxicity; (ii) activation of anti-genotoxicity pathways were associated with chemotherapy cardiotoxicity; (iii) quantitative trait loci (QTLs) specific and common to cardiotoxicity and the levels of the pathways studied. [Conclusion]: We identified genetic determinants associated with anthracycline cardiotoxicity using components of the anti-genotoxic pathways as subphenotypes. Crosses of syngeneic mouse strains are useful in these studies, but require further validation in the human population.
DescripciónResumen del póster presentado al XXXIX Congreso de la Sociedad Española de Bioquímica y Biología Molecular, celebrado en Salamanca del 5 al 8 de septiembre de 2016.
URIhttp://hdl.handle.net/10261/169551
Aparece en las colecciones: (IBMCC) Comunicaciones congresos
Ficheros en este ítem:
Fichero Descripción Tamaño Formato  
accesoRestringido.pdf15,38 kBAdobe PDFVista previa
Visualizar/Abrir
accesoRestringido.pdf15,38 kBAdobe PDFVista previa
Visualizar/Abrir
Mostrar el registro completo
 


NOTA: Los ítems de Digital.CSIC están protegidos por copyright, con todos los derechos reservados, a menos que se indique lo contrario.