論文 - 詳細
| RRC ID | 42122 |
|---|---|
| 著者 | Choi S, Nishikawa M, Sakoda A, Sakai Y. |
| タイトル | Feasibility of a simple double-layered coculture system incorporating metabolic processes of the intestine and liver tissue: application to the analysis of benzo[a]pyrene toxicity. |
| ジャーナル | Toxicol In Vitro |
| Abstract |
A simple double-layered coculture system using Caco-2 cell and Hep G2 cell, which mimic metabolic processes occurring in humans such as absorption through the intestine and cytochrome P450 1A1/2 involving biotransformation in both the intestine and liver cells, was used to investigate the toxicity of model chemical, benzo[a]pyrene (B[a]P). It was found that both Caco-2 and Hep G2 cells can metabolize B[a]P to toxic metabolites including B[a]P-7,8-hydrodiol (7,8-diol), an immediate precursor to the highly-reactive ultimate toxicant of B[a]P, B[a]P-7,8-hydrodiol-9,10-epoxide (BPDE), possibly mediated by cytochrome P450 1A1/2 activity. However, in a double-layered coculture system, no significant reduction of Hep G2 cell viability was found, although an approximately 50% reduction in viability was observed in pure Hep G2 cells. HPLC analysis showed that Caco-2 cells transfer B[a]P and its toxic metabolites back to the apical side, thus decreasing the concentrations of toxic metabolites including B[a]P-7,8-hydrodiol (7,8-diol) in cocultured Hep G2 cells. These results appear to be correlated with in vivo data on the effects of orally administered B[a]P, that is, low (10%) bioavailability in the rats and almost no acute lethal toxicity in rats or mice. As such, the simple double-layered coculture system can provide more accurate information regarding the toxic actions of the hazardous chemicals in humans than a pure culture system, as it also gives the final toxicity as a result of many complicated phenomena such as selective permeation in the intestine and biotransformation in the intestine and liver. |
| 巻・号 | 18(3) |
| ページ | 393-402 |
| 公開日 | 2004-6-1 |
| DOI | 10.1016/j.tiv.2003.09.010 |
| PII | S0887233303002297 |
| PMID | 15046787 |
| MeSH | Benzo(a)pyrene / metabolism Benzo(a)pyrene / toxicity* Biotransformation Caco-2 Cells Caffeine / toxicity Cell Line, Tumor Cell Survival / drug effects* Coculture Techniques Cytochrome P-450 CYP1A1 / metabolism Cytochrome P-450 CYP1A2 / metabolism Humans Intestinal Mucosa / metabolism Liver / metabolism Methylcholanthrene Toxicity Tests / methods* |
| IF | 2.959 |
| 引用数 | 39 |
| WOS 分野 | TOXICOLOGY |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | Patent(IFI CLAIMS) |
| 各媒体での言及数の合計 | 26 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 3.0 |
| リソース情報 | |
| ヒト・動物細胞 | Hep G2(RCB1648) |