caa a22 4500 44529230X CHVBK 20180317142532.0 cr unu---uuuuu 170323e20100101xx s 000 0 eng 10.1007/s11626-009-9244-z doi (NATIONALLICENCE)springer-10.1007/s11626-009-9244-z Cytochrome P450 expression profile of the PICM-19H pig liver cell line: potential application to rapid liver toxicity assays [Elektronische Daten] [Ryan Willard, Nancy Shappell, John Meekin, Neil Talbot, Thomas Caperna] Liver in vitro models are needed to replace animal models for rapid assessment of drug biotransformation and toxicity. The PICM-19 pig liver stem cell line may fulfill this need since these cells have activities associated with xenobiotic phase I and II metabolism lacking in other liver cell lines. The objective of this study was to characterize phase I and II metabolic functions of a PICM-19 derivative cell line, PICM-19H, compared to the tumor-derived human HepG2 C3A cell line and primary cultures of adult porcine hepatocytes. Following exposure of PICM-19H cells to either 3-methylcholanthrene, rifampicin or phenobarbital, the induced activities of cytochrome P450 (CYP450) isozymes CYP-1A, -2, and-3A were assessed. Relative to adult porcine hepatocytes, PICM-19H cells exhibited 30% and 43%, respectively, of CYP1A and 3A activities, while HepG2 C3A cells exhibited 7% and 0% of those activities. Fluorescent metabolites were extensively conjugated, i.e., 52% and 96% of CYP450-1A and-3A metabolites were released from medium samples following treatment with β-glucuronidase/arylsulfatase. Rifampicin induction of CYP450 isozyme activities was confirmed by conversion of testosterone to 6β-OH-, 2α-OH- and 2β-OH-testosterone, as determined by mass spectrometry. Susceptibility of PICM-19H cells to acetaminophen toxicity was determined; CD50 was calculated to be 14.9 ± 0.9mM. Toxicity and bioactivation of aflatoxin B1 was determined in 3-methylcholanthrene-treated cultures and untreated controls; CD50 were 1.59μM and 31μM, respectively. These results demonstrate the potential use of PICM-19H cells in drug biotransformation and toxicity testing and further support their use in extracorporeal artificial liver device technology. The Society for In Vitro Biology, 2009 Cell nationallicence Cytochrome nationallicence Liver nationallicence Hepatocyte nationallicence Toxicology nationallicence Willard Ryan USDA, ARS, Animal and Natural Resources Institute, Animal Biosciences and Biotechnology Laboratory, Beltsville Agricultural Research Center, Bldg. 200, Rm. 13, BARC-East, 20705, Beltsville, MD, USA aut Shappell Nancy USDA-ARS, Animal Metabolism Unit, Biosciences Research Laboratory, 58105, Fargo, ND, USA aut Meekin John Hepalife Technologies, Inc., 60 State Street, Suite 700, 02109, Boston, MA, USA aut Talbot Neil USDA, ARS, Animal and Natural Resources Institute, Animal Biosciences and Biotechnology Laboratory, Beltsville Agricultural Research Center, Bldg. 200, Rm. 13, BARC-East, 20705, Beltsville, MD, USA aut Caperna Thomas USDA, ARS, Animal and Natural Resources Institute, Animal Biosciences and Biotechnology Laboratory, Beltsville Agricultural Research Center, Bldg. 200, Rm. 13, BARC-East, 20705, Beltsville, MD, USA aut In Vitro Cellular & Developmental Biology - Animal Springer-Verlag 46/1(2010-01-01), 11-19 1071-2690 46:1<11 2010 46 11626 https://doi.org/10.1007/s11626-009-9244-z text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s11626-009-9244-z text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Willard Ryan USDA, ARS, Animal and Natural Resources Institute, Animal Biosciences and Biotechnology Laboratory, Beltsville Agricultural Research Center, Bldg. 200, Rm. 13, BARC-East, 20705, Beltsville, MD, USA aut NATIONALLICENCE 700 1- Shappell Nancy USDA-ARS, Animal Metabolism Unit, Biosciences Research Laboratory, 58105, Fargo, ND, USA aut NATIONALLICENCE 700 1- Meekin John Hepalife Technologies, Inc., 60 State Street, Suite 700, 02109, Boston, MA, USA aut NATIONALLICENCE 700 1- Talbot Neil USDA, ARS, Animal and Natural Resources Institute, Animal Biosciences and Biotechnology Laboratory, Beltsville Agricultural Research Center, Bldg. 200, Rm. 13, BARC-East, 20705, Beltsville, MD, USA aut NATIONALLICENCE 700 1- Caperna Thomas USDA, ARS, Animal and Natural Resources Institute, Animal Biosciences and Biotechnology Laboratory, Beltsville Agricultural Research Center, Bldg. 200, Rm. 13, BARC-East, 20705, Beltsville, MD, USA aut NATIONALLICENCE 773 0- In Vitro Cellular & Developmental Biology - Animal Springer-Verlag 46/1(2010-01-01), 11-19 1071-2690 46:1<11 2010 46 11626 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer