Reprint of: A three-dimensional in vitro HepG2 cells liver spheroid model for genotoxicity studies

Mutation Research. Genetic Toxicology and Environmental Mutagenesis
Ume-Kulsoom ShahGareth J S Jenkins

Abstract

The liver's role in metabolism of chemicals makes it an appropriate tissue for toxicity testing. Current testing protocols, such as animal testing and two-dimensional liver cell systems, offer limited resemblance to in vivo liver cell behaviour, in terms of gene expression profiles and metabolic competence; thus, they do not always accurately predict human toxicology. In vitro three-dimensional liver cell models offer an attractive alternative. This study reports on the development of a 3D liver model, using HepG2 cells, by a hanging-drop technique, with a focus on evaluating spheroid growth characteristics and suitability for genotoxicity testing. The cytokinesis-blocked micronucleus assay protocol was adapted to enable micronucleus (MN) detection in the 3D spheroid models. This involved evaluating the difference between hanging vs non-hanging drop positions for dosing of the test agents and comparison of automated Metafer scoring with manual scoring for MN detection in HepG2 spheroids. The initial seeding density, used for all experiments, was 5000 cells/20 μl drop hanging spheroids, harvested on day 4, with >75% cell viability. Albumin secretion (7.8 g/l) and both CYP1A1 and CYP1A2 gene expression were highest in the 3D envi...Continue Reading

Citations

Apr 19, 2021·Toxicology Letters·Nicholas J ColtmanNikolas J Hodges
Nov 5, 2020·ACS Biomaterials Science & Engineering·Christy ChaoBevin P Engelward

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