Phenobarbital, dexamethasone and benzanthracene induce several cytochrome P450 mRNAs in rat hepatoma cells

Abstract

Hepatoma cells derived from the Reuber H35 rat hepatoma express cytochrome P450 enzymes of two major families: polycyclic aromatic hydrocarbon-inducible forms are found in both differentiated and dedifferentiated cells while phenobarbital (PB)-inducible forms are found only in differentiated cells. We report here that (i) benzanthracene and PB induce P450 c mRNA in differentiated and dedifferentiated cells and (ii) dexamethasone and PB induce P450 b/e and/or P450 PBI mRNAs in differentiated cells but not in dedifferentiated cells.

Interleukin‐1β antagonizes phenobarbital induction of several major cytochromes P450 in adult rat hepatocytes in primary culture

“…ILl`0 could significantly, although modestly, lower basal mRNA accumulation levels of CYP2C and CYP2EI throul~hout the 7 experiments conducted in the present study. As previously described in various other model systems [34,35,[37][38][39][40], PB was able to induce EROD activity, as well as CYPIAI mRNA level. We also observed induction in hepatocytes cultured in Williams' E medium (data not shown).…”

Cell Lines: A Tool for In Vitro Drug Metabolism Studies

“…Hepatoma cell lines also express conjugating enzymes, namely glutathione S-transferase (GST) and UDP-glucuronyltransferase (UGT) and sulphotranferases ( Table 1) [14,15,[25][26][27][28]. For instance, KYN-2 and Mz-Hep-1 cells express one of the two different UGT isoforms found in hepatocytes [20].…”

Phenobarbital induction of cytochrome P-450 gene expression

“…Also of some usefulness as a model system may be the gene encoding P-450 2C6 (CYP2C6) (Umeno et al, 1988), whose mRNA can be induced by PB 2-4-fold in vivo (Friedberg et al, 1986) and is highly responsive to PB in several differentiated rat hepatoma cell lines (Corcos & Weiss, 1988). Finally, an examination of P-450 genes that are homologous to P-450s 2B1 and 2B2 but are not PB-inducible, such as rat P-450 2B3 (Labbe et al, 1988), may provide further insight into the molecular mechanisms that govern the selectivity of PB induction for individual P-450 genes.…”