ArticleToxicological sciences : an official journal of the Society of Toxicology2012
Determination of drug toxicity using 3D spheroids constructed from an immortal human hepatocyte cell line.
Article in Toxicological sciences : an official journal of the Society of Toxicology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 79 papers.
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Who cites it
79 citing papers in PubMed.
- New Approach Methodologies (NAMs) in Alternative Methods: A Comparative Cytotoxicity Analysis of Nanostructured Hydroxyapatite in Adipose Stem Cells Spheroids.Journal of applied toxicology : JAT · 2026Article
- A Machine Vision-Guided Microphysiological Platform With Automated Microfluidics Enables Longitudinal Biomarker Monitoring and Emulation of Translationally Relevant Exposure Scenarios.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Physiologically relevant 3D CRISPR screening enhances mechanistic insight into chemical toxicity compared to 2D screening.Toxicology · 2026Article
- Physiologically Relevant 3D CRISPR Screening Enhances Mechanistic Insight into Chemical Toxicity Compared to 2D Screening.bioRxiv : the preprint server for biology · 2025Article
- Induced Extracellular Ice Nucleation Protects Cocultured Spheroid Interior and Exterior during Cryopreservation.ACS biomaterials science & engineering · 2025Article
- Gamma secretase inhibitors, DAPT and MK0752, exhibit synergistic anticancer effects with cisplatin and docetaxel in 2D and 3D models of breast cancer.Turkish journal of biology = Turk biyoloji dergisi · 2025Article
- Unlocking Nature's Potential: Ferritin as a Universal Nanocarrier for Amplified Cancer Therapy Testing via 3D Microtissues.ACS applied materials & interfaces · 2024Article
- Review
- Article
- CrossFuse-XGBoost: accurate prediction of the maximum recommended daily dose through multi-feature fusion, cross-validation screening and extreme gradient boosting.Briefings in bioinformatics · 2023Article
- Cryopreservation of assay-ready hepatocyte monolayers by chemically-induced ice nucleation: preservation of hepatic function and hepatotoxicity screening capabilities.Biomaterials science · 2023Article
- Article
- Technology platform for facile handling of 3D hydrogel cell culture scaffolds.Scientific reports · 2023Article
- Article
- Proline-conditioning and chemically-programmed ice nucleation protects spheroids during cryopreservation.Chemical communications (Cambridge, England) · 2023Article
- Article
- Newly developed 3D in vitro models to study tumor-immune interaction.Journal of experimental & clinical cancer research : CR · 2023Review
- Combined Toxic Effects of BPA and Its Two Analogues BPAP and BPC in a 3D HepG2 Cell Model.Molecules (Basel, Switzerland) · 2023Article
- Liver three-dimensional cellular models for high-throughput chemical testing.Cell reports methods · 2023Review
- Review
19 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
2 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Numerous publications have documented that the immortal cells grown in three-dimensional (3D) cultures possess physiological behavior, which is more reminiscent of their parental organ than when the same cells are cultivated using classical two-dimensional (2D) culture techniques. The goal of this study was to investigate whether this observation could be extended to the determination of LD(50) values and whether 3D data could be correlated to in vivo observations. We developed a noninvasive means to estimate the amount of protein present in a 3D spheroid from it is planar area (± 21%) so that a precise dose can be provided in a manner similar to in vivo studies. This avoided correction of the actual dose given based on a protein determination after treatment (when some cells may have lysed). Conversion of published in vitro LC(50) data (mM) for six common drugs (acetaminophen, amiodarone, diclofenac, metformin, phenformin, and valproic acid) to LD(50) data (mg compound/mg cellular protein) showed that the variation in LD(50) values was generally less than that suggested by the original LC(50) data. Toxicological analysis of these six compounds in 3D spheroid culture (either published or presented here) demonstrated similar LD(50) values. Although in vitro 2D HepG2 data showed a poor correlation, the primary hepatocyte and 3D spheroid data resulted in a much higher degree of correlation with in vivo lethal blood plasma levels. These results corroborate that 3D hepatocyte cultures are significantly different from 2D cultures and are more representative of the liver in vivo.
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