Quantitative comparison of in vitro genotoxicity between metabolically competent HepaRG cells and HepG2 cells using the high-throughput high-content CometChip assay

Archives of Toxicology
Ji-Eun SeoXiaoqing Guo

Abstract

In vitro genotoxicity testing that employs metabolically active human cells may be better suited for evaluating human in vivo genotoxicity than current bacterial or non-metabolically active mammalian cell systems. In the current study, 28 compounds, known to have different genotoxicity and carcinogenicity modes of action (MoAs), were evaluated over a wide range of concentrations for the ability to induce DNA damage in human HepG2 and HepaRG cells. DNA damage dose-responses in both cell lines were quantified using a combination of high-throughput high-content (HTHC) CometChip technology and benchmark dose (BMD) quantitative approaches. Assays of metabolic activity indicated that differentiated HepaRG cells had much higher levels of cytochromes P450 activity than did HepG2 cells. DNA damage was observed for four and two out of five indirect-acting genotoxic carcinogens in HepaRG and HepG2 cells, respectively. Four out of seven direct-acting carcinogens were positive in both cell lines, with two of the three negatives being genotoxic mainly through aneugenicity. The four chemicals positive in both cell lines generated HTHC Comet data in HepaRG and HepG2 cells with comparable BMD values. All the non-genotoxic compounds, including s...Continue Reading

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Citations

Nov 21, 2019·Journal of Toxicology and Environmental Health. Part B, Critical Reviews·Xiaoqing GuoNan Mei
Mar 12, 2020·Toxicological Sciences : an Official Journal of the Society of Toxicology·Xilin LiNan Mei
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Sep 29, 2020·Journal of Toxicology and Environmental Health. Part a·Xiaoqing GuoNan Mei
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Apr 16, 2021·Toxicological Sciences : an Official Journal of the Society of Toxicology·Ji-Eun SeoMugimane G Manjanatha
Nov 10, 2020·Toxicology in Vitro : an International Journal Published in Association with BIBRA·D DesaulniersC Parfett
Nov 5, 2020·ACS Biomaterials Science & Engineering·Christy ChaoBevin P Engelward

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Methods Mentioned

BETA
chromosomal aberration
electrophoresis
chip
chemical treatment
chemical treatments

Software Mentioned

Leica application suite
SigmaPlot
Trevigen Comet Analysis
R
PROAST

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