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2021-06-12 - Article/Dans un journal avec peer-review - Anglais - 15 page(s)

Nachtergael Amandine , Lanterbecq Deborah, Spanoghe Martin, Belayew Alexandra , Duez Pierre , "Effects of chemopreventive natural compounds on the accuracy of 8-oxo-7,8-dihydro-2'-deoxyguanosine translesion synthesis" in Planta Medica, Accepté pour publication

  • Edition : Georg Thieme Verlag (Germany)
  • Codes CREF : Chimie analytique (DI1314), Pharmacognosie (DI3410), Sciences pharmaceutiques (DI3400), Toxicologie pharmaceutique (DI3440)
  • Unités de recherche UMONS : Chimie thérapeutique et Pharmacognosie (M136)
  • Instituts UMONS : Institut des Sciences et Technologies de la Santé (Santé), Institut des Biosciences (Biosciences)
Texte intégral :

Abstract(s) :

(Anglais) Translesion synthesis (TLS) is a DNA damage tolerance mechanism that relies on a series of specialized DNA polymerases able to bypass a lesion on a DNA template strand during replication or post-repair synthesis. Specialized TLS DNA polymerases pursue replication by inserting a base opposite to this lesion, correctly or incorrectly depending on the lesion nature, involved DNA polymerase(s), sequence context and still unknown factors. To measure the correct or mutagenic outcome of 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) bypass by TLS, a primer-extension assay was performed in vitro on a template DNA bearing this lesion in the presence of nuclear proteins extracted from human intestinal epithelial cells (FHs 74 Int cell line); the reaction products were analysed by both denaturing capillary electrophoresis (to measure the yield of translesion elongation) and pyrosequencing (to determine the identity of the nucleotide inserted in front of the lesion). The influence of 14 natural polyphenols on the correct or mutagenic outcome of TLS through 8-oxodG was then evaluated, in two experimental conditions, by adding the polyphenol either (i) to the reaction mix during the primer extension assay; or (ii) to the culture medium, 24 h before cell harvest and nuclear proteins extraction. Most of the tested polyphenols significantly influenced the outcome of translesion synthesis, either through an error-free (apigenin, baicalein, sakuranetin and myricetin) or a mutagenic pathway (epicatechin, chalcone, genistein, magnolol and honokiol).