Performance of high-throughput CometChip assay using primary human hepatocytes: a comparison of DNA damage responses with in vitro human hepatoma cell lines.
Benchmark dose
CometChip assay
HepG2 cells
HepaRG cells
Primary human hepatocytes
Journal
Archives of toxicology
ISSN: 1432-0738
Titre abrégé: Arch Toxicol
Pays: Germany
ID NLM: 0417615
Informations de publication
Date de publication:
06 2020
06 2020
Historique:
received:
07
02
2020
accepted:
06
04
2020
pubmed:
23
4
2020
medline:
13
7
2021
entrez:
23
4
2020
Statut:
ppublish
Résumé
Primary human hepatocytes (PHHs) are considered the "gold standard" for evaluating hepatic metabolism and toxicity of xenobiotics. In the present study, we evaluated the genotoxic potential of four indirect-acting (requiring metabolic activation) and six direct-acting genotoxic carcinogens, one aneugen, and five non-carcinogens that are negative or equivocal for genotoxicity in vivo in cryopreserved PHHs derived from three individual donors. DNA damage was determined over a wide range of concentrations using the CometChip technology and the resulting dose-responses were quantified using benchmark dose (BMD) modeling. Following a 24-h treatment, nine out of ten genotoxic carcinogens produced positive responses in PHHs, while negative responses were found for hydroquinone, aneugen colchicine and five non-carcinogens. Overall, PHHs demonstrated a higher sensitivity (90%) for detecting DNA damage from genotoxic carcinogens than the sensitivities previously reported for HepG2 (60%) and HepaRG (70%) cells. Quantitative analysis revealed that most of the compounds produced comparable BMD
Identifiants
pubmed: 32318794
doi: 10.1007/s00204-020-02736-z
pii: 10.1007/s00204-020-02736-z
doi:
Substances chimiques
Mutagens
0
Types de publication
Comparative Study
Journal Article
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Pagination
2207-2224Références
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