Elsevier

Methods in Enzymology

Volume 272, 1996, Pages 388-401
Methods in Enzymology

[42] Use of human hepatocytes to study P450 gene induction

https://doi.org/10.1016/S0076-6879(96)72044-XGet rights and content

Publisher Summary

The human hepatocyte model system is useful for investigations of interspecies and interindividual differences in P450-related activities, including induction of gene expression in response to xenobiotic exposure and the molecular events controlling gene expression through the transfection of reporter gene constructs. The CYP3A family is the major steroid-inducible cytochrome P450s in rats, rabbits, and humans. No single animal model faithfully predicts the responses observed in human hepatocyte preparations. Hepatocytes can be cryopreserved and reestablished into culture, and the frozen/thawed cells still respond to P450-inducing compounds with enhanced gene transcription and drug-metabolizing capacity. It is crucial to gain a complete understanding of the genetic structure, regulation, and functional activity of human cytochrome P450s because of the relative importance of cytochrome P450s in the biotransformation of a variety of exogenous and endogenous compounds.

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    Circulating plasma GH profiles were determined by a sensitive sandwich ELISA method according to Steyn et al. (2011) with modifications by us (Das et al., 2013). Preparation of hepatocytes from control and neonatally MSG-treated adult rats were performed with minor modifications (Thangavel et al., 2006; Thangavel and Shapiro, 2007) by in situ perfusion of collagenase through the portal vein of the anesthetized rats following standard protocol (Strom et al., 1996). The viability of the initial cell suspension of hepatocytes was typically between 80 and 90% (with trypan blue).

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