DNA-AP sites generation by etoposide in whole blood cells.

BMC Cancer
Emilio RojasMahara Valverde

Abstract

Etoposide is currently one of the most commonly used antitumor drugs. The mechanisms of action proposed for its antitumor activity are based mainly on its interaction with topoisomerase II. Etoposide effects in transformed cells have been described previously. The aim of the present study was to evaluate the genotoxic effects of this drug in non-transformed whole blood cells, such as occurs as collateral damage induced by some chemotherapies. To determine etoposide genotoxicity, we employed Comet assay in two alkaline versions. To evaluate single strand breaks and delay repair sites we use pH 12.3 conditions and pH >13 to evidence alkali labile sites. With the purpose to quantified apurinic or apyrimidine (AP) sites we employed a specific restriction enzyme. Etoposide effects were determined on whole blood cells cultured in absence or presence of phytohemagglutinin (PHA) treated during 2 and 24 hours of cultured. Alkaline (pH > 13) single cell gel electrophoresis (SCGE) assay experiments revealed etoposide-induced increases in DNA damage in phytohemaglutinine (PHA)-stimulated blood and non-stimulated blood cells. When the assay was performed at a less alkaline pH, 12.3, we observed DNA damage in PHA-stimulated blood cells consi...Continue Reading

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Citations

Dec 23, 2011·Oxidative Medicine and Cellular Longevity·Silva-Aguilar MartínValverde Mahara
Dec 10, 2013·Environmental Toxicology·Juan J Rodríguez-MercadoMario A Altamirano-Lozano
Nov 21, 2020·Food and Chemical Toxicology : an International Journal Published for the British Industrial Biological Research Association·Damián MuruzabalAmaya Azqueta

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