Currently we are planning qPCR gene expression studies of the biotransformation system of our hepatocyte-derived cell line from cattle.
What would be suitable CYP inducers beside beta-naphtoflavon for CYP1A1 and dexamethasone for CYP3A?. Is there any possibilty to induce phase II biotransformation enzymes like UGT1? What CYPs and phase II enzymes are espacially important in cattle and should be definitly attested?
Thank you for your help.
We used several inducers for the CYP-system in different cell lines, such as ethanol (CYP2E1), benzo[a]pyrene and other PAH for CYP1A1 (works better than beta-naphtholavone), phenobarbital for CYP2B, clotrimazole and dexamthasone for CYP3A and clofibrate for CYP4-enzymes. While all of these compounds work in the animal, this can not be true for cell lines. In some cases they are 'resistent', in other cases unusual enzymes are induced - i.e. other CYPs than expected.
Peter
Dear Alexander,
Our life-long experimentation with phase I and phase II biotransformation enzymes allows me advising you on TCDD as a very potent inducer for UGT1. Namely, the AhR gene/protein battery members (and coregulated Nrf2 enzymes) are involved in the UGT1 gene family, including human one. We investigated mechanisms responsible for regulation of human UGT1 by AhR and by antioxidant-inducible Nrf2. The recent finding of Nrf2 as a downstream target of the AhR explain earlier observation that the AhR plays a major role in the control of tBHQ-induced UGT1 activity: UGT1 activity was induced by both TCDD and tBHQ in studies with rat hepatoma 5L cells; induction was was also demonstrated in AhR-complemented cells.
Best wishes,
Ilya
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