Back to Search
Start Over
Performance of comet and micronucleus assays in metabolic competent HepaRG cells to predict in vivo genotoxicity
- Source :
- Review of Economic Dynamics, Review of Economic Dynamics, Elsevier, 2014, epub ahead of print. ⟨10.1093/toxsci/kfu004⟩
- Publication Year :
- 2014
-
Abstract
- Genetic toxicity information is critical for the safety assessment of all xenobiotics. In the absence of carcinogenicity data, genetic toxicity studies may be used to draw conclusions about the carcinogenicity potential of chemicals. However, current in vitro assays have many limitations as they produce a high rate of irrelevant positive data and possible false negative data due to the weakness of the in vitro models used. Based on the knowledge that the majority of human genotoxic carcinogens require metabolic activation to become genotoxic, it is necessary to develop in vitro cell models that mimic human liver metabolism to replace the use of liver S9 fraction, which, though helpful for predicting the potential carcinogenicity of chemicals in rodents, is questionable in humans. We therefore investigate whether the recently described human hepatoma HepaRG cells, which express the major characteristics of liver functions similarly to primary human hepatocytes, could be a suitable model for human genotoxicity assessment. We determine the performance of comet and micronucleus assays in HepaRG cells to predict in vivo genotoxins based on the list of compounds published by European Centre for the Validation of Alternative Methods (ECVAM). Twenty compounds were tested in HepaRG cells with comet and micronucleus assays over a 24-h period. The specificity, the sensitivity, and the accuracy of the two tests were determined. We found that the comet assay had higher specificity (100%) than the micronucleus (MN) test (80%), whereas the latter was far more sensitive (73%) than the former (44%), resulting nonetheless in an accuracy of 72% for the comet assay and 75% for the MN test. Taken together, our data suggest that the HepaRG cell line can be of use in genetic toxicology and that efforts to develop competent human liver cell models should be increased.
- Subjects :
- Biology
medicine.disease_cause
Sensitivity and Specificity
03 medical and health sciences
0302 clinical medicine
Cytochrome P-450 Enzyme System
In vivo
toxicological test
Predictive Value of Tests
Cell Line, Tumor
medicine
Humans
Carcinogen
Micronuclei, Chromosome-Defective
030304 developmental biology
Genetics
Cryopreservation
0303 health sciences
Micronucleus Tests
In vitro toxicology
toxicologie
3. Good health
Comet assay
S9 fraction
Liver
030220 oncology & carcinogenesis
[SDV.TOX]Life Sciences [q-bio]/Toxicology
Micronucleus test
Cancer research
Comet Assay
Micronucleus
Genotoxicity
toxicology
DNA Damage
Mutagens
Subjects
Details
- ISSN :
- 10960929 and 10942025
- Volume :
- 138
- Issue :
- 2
- Database :
- OpenAIRE
- Journal :
- Toxicological sciences : an official journal of the Society of Toxicology
- Accession number :
- edsair.doi.dedup.....5a16fad591d4ccb6a6b0750ba3702c05