Effect of the anti-neoplastic drug doxorubicin on XPD-mutated DNA repair-deficient human cells

Doxorubicin (DOX), a member of the anthracycline group, is a widely used drug in cancer therapy. The mechanisms of DOX action include topoisomerase II-poisoning, free radical release, DNA adducts and interstrand cross-link (ICL) formation. Nucleotide excision repair(NER) is involved in the removal of helix-distorting lesions and chemical adducts, however, little is known about the response of NER-deficient cell lines to anti-tumoral drugs like DOX. Wild type and XPD-mutated cells, harbouring mutations in different regions of this gene and leading to XP-D, XP/CS or TTD diseases, were treated with this drug and analyzed for cell cycle arrest and DNA damage by comet assay. The formation of DSBs was also investigated by determination of gamma H2AX foci. Our results indicate that all three NER-deficient cell lines tested are more sensitive to DOX treatment, when compared to wild type cells or XP cells complemented by the wild type XPD cDNA, suggesting that NER is involved in the removal of DOX-induced lesions. The cell cycle analysis showed the characteristic G2 arrest in repair-proficient MRC5 cell line after DOX treatment, whereas the repair-deficient cell lines presented significant increase in sub-G1 fraction. The NER-deficient cell lines do not show different patterns of DNA damage formation as assayed by comet assay and phosphorylated H2AX foci formation. Knock-down of topoisomerase II alpha with siRNA leads to increased survival in both MRC5 and XP cells, however, XP cell line still remained significantly more sensitive to the treatment by DOX. Our study suggests that the enhanced sensitivity is due to DOX-induced DNA damage that is subject to NER, as we observed decreased unscheduled DNA synthesis in XP-deficient cells upon DOX treatment. Furthermore, the complementation of the XPD-function abolished the observed sensitivity at lower DOX concentrations, suggesting that the XPD helicase activity is involved in the repair of DOX-induced lesions. (C) 2009 Elsevier B.V. All rights reserved.

Public Drinking in the Early Modern World: Voices from the Tavern, 1500-1800

Until recently the role of the public drinking house has been approached from elitist, folkloric and anecdotal perspectives. The work of a new generation of social historians, however, has raised the tavern’s profile in the academic consciousness and confirmed its position within the mainstream of social and cultural history. It is now recognized that an understanding of the centrality of public drinking to the development of both elite and popular culture is vital to studies of social behaviour. The study of taverns has also been at the forefront of emerging interest in the history of consumption and material culture, and has contributed to a richer understanding of economic history. Constructions of gender and identity are also visible through research into the patterns of behaviour and discourse in and around the public house. This four-volume reset edition presents a wide-ranging collection of primary sources which uncover the language and behaviour of local and state authorities, of peasants and town-dwellers, and of drinking companions and irate wives. The documents are translated and set in their social and historical context, providing a multidisciplinary collection that will be of great importance to scholars of all areas of social and cultural history of the early modern period. The vast majority of this material is published here for the first time, ensuring that the collection will open up new avenues of research. Volume 1 draws heavily from the Parisian police archives and includes inspectors’ reports, complaints by the general public and details of court cases to build a picture of drinking in early modern France. Volumes 2 and 3 address public drinking in the Holy Roman Empire through a variety of chronicles, civic ordinances, court records, travel reports and surveys of public houses. Volume 4 locates taverns within a broader analysis of America’s public houses, drawing on visual material as well as journal entries, business reports and newspaper articles. Each volume is accompanied by editorial introductions and is annotated to provide readers with a high-quality resource of scholarly material.

Réimpression de l'ancien Moniteur : seule histoire authentique et inaltérée de la révolution française depuis la réunion des États-généraux jusqu'au Consulat (mai 1789-novembre 1799) /

Introduction historique.--t. 1-6. Assemblée constituante.--t. 7-9. Constituante.--t. 10-13. Assemblée législative.--t. 14-25. Convention nationale.--t. 26. Convention nationale. Directoire.--t. 27-29. Directoire exécutif.--t. 30-31. Ray, M. A. Table.

Archives parlementaires de 1787 à 1860.

Mode of access: Internet.

Histoire de la révolution française.

Half-title; author's name on individual title-pages.

Histoire du règne de Louis XVI, pendant les années où l'on pouvait prévenir ou diriger la révolution française;

Vol. 3: Appendice. Mirabeau et l'Assemblee constituante.

Archives parlementaires de 1787 à 1860; recueil complet des débats législatifs et politiques des chambres françaises.

Mode of access: Internet.

Programmes des cours ... : précédés d'une notice sur l'enseignement de l'école /

Mode of access: Internet.

Souvenirs sur Mirabeau et sur les deux premières assemblées législatives,

Mode of access: Internet.

Scelta di commedie /

Pamela. -La villegiatura. -Il burbero benefico. -Il vero amico. -La scozzese. -Gli amori di Zelinda e Lindoro. -Corrispondenza fra il conte Albergati, Voltaire e Goldoni. -Rapport de Chénier à la Convention nationale relativement à la pension à accorder à Goldoni.

Histoire de la gendarmerie, depuis sa créatin jusqu'en 1790.

Mode of access: Internet.