| A co-culture system of human intestinal Caco-2 cells and lymphoblastoid TK6 cells for investigating the genotoxicity of oral compounds. | |
| | |
MedLine Citation:
|
PMID: 22844081 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
|
Here, we assessed a co-culture system of intestinal Caco-2 cells and lymphoblastoid TK6 cells for modelling the role of intestinal first-pass effects, i.e. absorption and metabolism, in the genotoxicity of oral drugs and food contaminants. Caco-2 cells were seeded onto semipermeable culture inserts for 21 days until differentiation, and then TK6 cells were added to the basal compartment. After apical loading with mutagenic compounds [methylmethanesulfonate (MMS), benzo[a]-pyrene (BaP) and aflatoxin B1 (AFB1)], comet and micronucleus assays were performed on both cell lines. MMS (10 µg/ml) showed positive results in the micronucleus assays in both cell lines, even though DNA damage was only detected in the Caco-2 cells with the comet assay. At concentrations of 0.5-50 µM, BaP induced dose-dependent comet and micronucleus formation at 24h in Caco-2 cells, but no DNA damage was observed in TK6 cells. Although AFB1 failed to induce comet formation, it resulted in a high level of micronuclei in both cell lines. Treatment of Caco-2 cells with the CYP3A4 inhibitor, ketoconazole, inhibited the AFB1-induced cytotoxicity and micronucleus formation in TK6 cells, suggesting that intestinal metabolism is involved in the AFB1 genotoxic response in TK6 cells. Our results suggest that the Caco-2/TK6 co-culture model is suitable for modelling the role of intestinal biotransformation and transport processes in the genotoxic potential of oral drugs and food contaminants in target blood cells. |
| | |
Authors:
|
Ludovic Le Hégarat; Sylvie Huet; Valérie Fessard |
Publication Detail:
|
Type: JOURNAL ARTICLE Date: 2012-7-27 |
Journal Detail:
|
Title: Mutagenesis Volume: - ISSN: 1464-3804 ISO Abbreviation: - Publication Date: 2012 Jul |
Date Detail:
|
Created Date: 2012-7-30 Completed Date: - Revised Date: - |
Medline Journal Info:
|
Nlm Unique ID: 8707812 Medline TA: Mutagenesis Country: - |
Other Details:
|
Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
|
ANSES, Laboratoire de Fougères, Unité de Toxicologie des contaminants BP 90203, 35302 Fougères Cedex, France. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
|
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Genotoxicity assessment and detoxification induction in Dreissena polymorpha exposed to benzo[a]pyre...
Next Document: What predicts persistent early conduct problems? Evidence from the Growing Up in Scotland cohort.