Drug metabolising activity of freshly isolated human hepatocytes.
Hepatocytes have been isolated from samples of adult human liver by removal of extracellular calcium followed by perfusion with collagenase. The hepatocytes were isolated with a yield of up to 39 X 10(6) cells/g and with a viability of up to 74%. The cells were active in the oxidation of aldrin and 7-ethoxycoumarin. They also catalysed the conjugation of 7-hydroxycoumarin. Monooxygenase activity of the hepatocytes was linear for at least 60 min. Maintenance of the hepatocytes in suspension at 4 degrees C for 19 h resulted in a 15% loss in viability. This was accompanied by a 50% decrease in monooxygenase activity expressed per viable cell. It is concluded that human hepatocytes can be isolated in sufficient yield and with satisfactory viability for use in a range of studies on drug metabolism and toxicity.
D015660:7-Alkoxycoumarin O-Dealkylase; D000328:Adult; D000368:Aged; D000452:Aldrin / Q000378:metabolism; D002470:Cell Survival; D003374:Coumarins / Q000378:metabolism; D003470:Culture Media; D004852:Epoxy Compounds / Q000378:metabolism; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D007700:Kinetics; D008099:Liver / Q000201:enzymology / Q000378:metabolism* / Q000648:ultrastructure; D008297:Male; D008854:Microscopy, Electron; D008875:Middle Aged; D006899:Mixed Function Oxygenases / Q000378:metabolism; D010105:Oxygenases / Q000378:metabolism; D004364:Pharmaceutical Preparations / Q000378:metabolism*
D003374:Coumarins; D003470:Culture Media; D004852:Epoxy Compounds; D004364:Pharmaceutical Preparations; C017299:7-ethoxycoumarin; D006899:Mixed Function Oxygenases; C019647:aldrin epoxidase; D010105:Oxygenases; D015660:7-Alkoxycoumarin O-Dealkylase; D000452:Aldrin