Uptake of taurocholate, a vecuronium-like organic cation, ORG 9426, and ouabain into carcinogen-induced diploid and polyploid hepatocytes obtained by centrifugal elutriation.
Bile acid uptake, an important function of differentiated hepatocytes, is decreased in hepatocellular carcinomas and gamma-glutamyltranspeptidase-positive, putatively preneoplastic hepatocytes. Whether hepatic uptake is also changed in carcinogen-induced diploid hepatocytes versus polyploid hepatocytes is unknown. The present study has determined whether the hepatic uptake of three model compounds, an anionic bile acid, an organic cation and a neutral organic compound, into diploid cells is different from that in polyploid hepatocytes. These two hepatocyte populations were separated from the parent freshly isolated hepatocyte suspension by centrifugal elutriation. Flow cytometric analysis indicated that the diploid fraction contained approximately 83% diploid cells and that the polyploid fraction had about 84% polyploid hepatocytes. Initial uptake velocity was determined for taurocholate (1-50 microM), ORG 9426 (20-400 microM), a vecuronium-like cation, and ouabain (20-500 microM). Apparent Km was not different between diploid and polyploid cells for the three tested substrates, whereas apparent Vmax was decreased in diploid hepatocytes for taurocholate and ouabain by 42 and 55%, respectively. There were no changes in the hepatic uptake of ORG 9426. These data indicate that uptake by the bile acid/multispecific carrier is compromised in carcinogen-induced diploid cells.
Schwarz
L R
LR
GSF-Institut für Toxikologie, Neuherberg, Federal Republic of Germany.
Watkins
J B
JB
D000732:Androstanols / Q000378:metabolism*; D000818:Animals; D002273:Carcinogens / Q000633:toxicity*; D002469:Cell Separation; D007700:Kinetics; D008099:Liver / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D008297:Male; D010042:Ouabain / Q000378:metabolism*; D011003:Ploidies; D051381:Rats; D011919:Rats, Inbred Strains; D000077123:Rocuronium; D013656:Taurocholic Acid / Q000378:metabolism*
D000732:Androstanols; D002273:Carcinogens; D010042:Ouabain; D013656:Taurocholic Acid; D000077123:Rocuronium