|Title||In vitro model for intestinal uptake of benzo(a)pyrene|
|Year of Publication||1999|
|Authors||Regine Goth-Goldstein, Hoi-Ying N Holman, Marion L Russell|
The human colon adenocarcinoma cell line, Caco-2, was used to study intestinal uptake of benzo(a)pyrene (BaP). BaP permeation was measured across Caco-2 monolayers grown on permeable supports that separate two chambers representing the intestinal lumen and the bloodstream. At high BaP concentration (10 μM) BaP permeation of the cell layer occurred at a linear rate. At lower and physiologically more relevant BaP concentrations (0.2 and 1 μM) permeation showed a more complex pattern with initial linear rate, then accelerated and finally reduced permeation. From the earliest sampling on (0.5 h) BaP permeation of the cell layer was accompanied by extensive metabolism to water soluble conjugates not extracted by organics. With 0.2 μM BaP about half the 3Hlabeled material appearing in the basolateral chamber consisted of BaP conjugates, and of the 3H-material extracted with organic solvents about half consisted of BaP metabolites. In addition we found that Caco-2 cells preferentially released metabolites into the apical chamber representing the intestinal lumen. We conclude that the intestinal epithelium is an important barrier that limits systemic availability of ingested BaP by presystemic detoxification and outwardly directed transport. We also conclude that the Caco-2 cell system is a useful in vitro model to predict systemic availability of xenobiotics in general.