Linked Life Data

15046787

Source:http://linkedlifedata.com/resource/pubmed/id/15046787

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2004-3-29
pubmed:abstractText
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.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
0887-2333
pubmed:author
pubmed:issnType
Print
pubmed:volume
18
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
393-402
pubmed:dateRevised
2009-4-10
pubmed:meshHeading
pubmed:year
2004
pubmed:articleTitle
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.
pubmed:affiliation
Institute of Industrial Science, University of Tokyo, 4-6-1 Komaba, Meguro-ku, Tokyo, 153-8505, Japan.
pubmed:publicationType
Journal Article, Comparative Study, Research Support, Non-U.S. Gov't