Cellular and Molecular Effects of Prolonged Low-Level Sodium Arsenite Exposure on Human Hepatic HepaRG Cells

Toxicological Sciences : an Official Journal of the Society of Toxicology
Kostiantyn DrevalIgor P Pogribny

Abstract

Inorganic arsenic is a human carcinogen associated with several types of cancers, including liver cancer. Inorganic arsenic has been postulated to target stem cells, causing their oncogenic transformation. This is proposed to be one of the key events in arsenic-associated carcinogenesis; however, the underlying mechanisms for this process remain largely unknown. To address this question, human hepatic HepaRG cells, at progenitor and differentiated states, were continuously treated with a noncytotoxic concentration of 1 μM sodium arsenite (NaAsO2). The HepaRG cells demonstrated active intracellular arsenite metabolism that shared important characteristic with primary human hepatocytes. Treatment of proliferating progenitor-like HepaRG cells with NaAsO2 inhibited their differentiation into mature hepatocyte-like cells, up-regulated genes involved in cell growth, proliferation, and survival, and down-regulated genes involved in cell death. In contrast, treatment of differentiated hepatocyte-like HepaRG cells with NaAsO2 resulted in enhanced cell death of mature hepatocyte-like cells, overexpression of cell death-related genes, and down-regulation of genes in the cell proliferation pathway, while biliary-like cells remained largely...Continue Reading

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Citations

Sep 15, 2020·Critical Reviews in Toxicology·Akin Cayir
Sep 1, 2018·Toxicological Sciences : an Official Journal of the Society of Toxicology·Ntube N O NgalameErik J Tokar
Aug 28, 2020·Archives of Toxicology·Volodymyr P TryndyakIgor P Pogribny
Dec 29, 2020·Basic & Clinical Pharmacology & Toxicology·Hongfang LiFushan Tang
Nov 10, 2020·Toxicology in Vitro : an International Journal Published in Association with BIBRA·D DesaulniersC Parfett
Jan 29, 2020·Chemical Research in Toxicology·Lok Ming TamYinsheng Wang
Oct 6, 2021·Human & Experimental Toxicology·Macario Martínez-CastilloAraceli Hernández-Zavala

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