The development of primary mammalian hepatocyte cultures and their use in toxicology

• Main Author: Poole, Alan
• Published: University of Surrey 1978
• Subjects: 615.9
• Online Access: https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.469200

Static and rotary cultures of adult mammalian hepatocytes have been routinely established from suspensions of monkey, rabbit and pig liver parenchymal cells isolated by means of a simplified, inexpensive recycling perfusion system. Light and electron microscope examination of the cultures showed that the hepatocytes appeared to retain similar morphological chacteristics of fully differentiated hepatic parenchymal cells for up to 5 days in static culture and up to 10 days in rotary culture, after which time they degenerated and were replaced by other cell types. The hepatocytes in both static and rotary culture, exhibited several major metabolic functions characteristic of liver in vivo, these included albumin synthesis, hippuric acid synthesis, urea production, bilirubin conjugation and responsiveness to insulin. The foreign metabolising capability of the cultured hepatocytes was typical of cytochrome P-450, not cytochrome P-448 as reported by other investigators, as witnessed by the metabolite profiles of biphenyl, aminopyrine, ethylmorphine, benzo/alpha/pyrene and 7-ethoxycoumarin. When exposed to inducing agents such as phenobarbitone a normal pattern of drug metabolising enzyme induction was observed. As the findings indicated that the hepatic parenchymal cells in both rotary and static culture were viable and behaved in many respects like normal adult liver in vivo investigations were undertaken to ascertain if such cultures could be used in in vitro bioassays for the detection of hepatotoxins and carcinogens.