title: Micro total bioassay system for ingested substances: assessment of intestinal absorption, hepatic metabolism, and bioactivity.
abstract: Oral medicines and food constituents are absorbed in the intestine and metabolized in the liver, after which they exhibit their activity toward a target tissue. Micromodels of human tissues were developed to mimic these processes and bioactivities. By integrating the micromodels, we realized a micro total bioassay system for oral substances; this system comprised a microintestine, microliver, and the target components. The microchip was composed of a slide glass and polydimethylsiloxane (PDMS) sheets with microchannels fabricated by photolithography. Caco-2 cells were cultured in the intestine component, and HepG2 cells, in the liver component. The human breast carcinoma MCF-7 cells were cultured in the target component, and the activities of anticancer agents and estrogen-like substances were successfully assayed. By using this system, the overall properties of the ingested cyclophosphamide, epirubicin, 17-β estradiol, and soy isoflavone, i.e., their intestinal absorption, hepatic metabolism, and bioactivity toward target cells, could be assayed with operative ease. Further, the assay time and cell consumption were reduced compared to those in conventional in vitro bioassay systems.
authors.affiliation: Department of Applied Biological Chemistry, School of Agricultural and Life Sciences, The University of Tokyo, 1-1-1 Yayoi, Bunkyo, Tokyo 113-8657, Japan.
authors.forename: Yuki
authors.initials: Y
authors.lastname: Imura
authors.forename: Kiichi
authors.initials: K
authors.lastname: Sato
authors.forename: Etsuro
authors.initials: E
authors.lastname: Yoshimura
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology; D045744:Cell Line, Tumor; D003520:Cyclophosphamide / Q000494:pharmacology; D015251:Epirubicin / Q000494:pharmacology; D004958:Estradiol / Q000494:pharmacology; D006801:Humans; D007408:Intestinal Absorption; D007529:Isoflavones / Q000494:pharmacology; D056656:Lab-On-A-Chip Devices; D008099:Liver / Q000378:metabolism*; D046208:Microchip Analytical Procedures / Q000379:methods*; D008954:Models, Biological
chemical_list: D000970:Antineoplastic Agents; D007529:Isoflavones; D015251:Epirubicin; D004958:Estradiol; D003520:Cyclophosphamide