Anticancer drug 5-fluorouracil induces reproductive and developmental defects in Caenorhabditis elegans. - Inserm - Institut national de la santé et de la recherche médicale Accéder directement au contenu
Article Dans Une Revue Reproductive Toxicology Année : 2010

Anticancer drug 5-fluorouracil induces reproductive and developmental defects in Caenorhabditis elegans.

Résumé

In order to examine the chronic effects of anticancer drug 5-fluorouracil (5-FU) on reproduction and development, we exploited Caenorhabditis elegans as a model system. We demonstrate that 5-FU induces cell-cycle arrest and apoptosis of germline cells and reduces by approximately 30-40% the number of mitotic nuclei per gonad arm when compared to untreated worms. This drug also affects vulva development, some animals being vulvaless, as well as dysfunction of vulval and egg laying muscles leading to an 8-10 days delay in reproductive time. Interestingly, 5-FU represses levels of mRNA encoding LIN-29, a transcription factor that affects vulva development and egg laying system. Finally, we demonstrate that RNAi-dependent repression of ung-1 gene, which encodes a uracil-DNA glycosylase, partially abolishes 5-FU effects on embryo hatching. Thus, we proposed that C. elegans could be a useful model system for studying the mechanisms by which 5-FU might affect either embryo, adult or organ development.

Dates et versions

inserm-00463900 , version 1 (15-03-2010)

Identifiants

Citer

Sandeep Kumar, Caroline Aninat, Grégoire Michaux, Fabrice Morel. Anticancer drug 5-fluorouracil induces reproductive and developmental defects in Caenorhabditis elegans.. Reproductive Toxicology, 2010, 29 (4), pp.415-20. ⟨10.1016/j.reprotox.2010.02.006⟩. ⟨inserm-00463900⟩
92 Consultations
0 Téléchargements

Altmetric

Partager

Gmail Facebook X LinkedIn More