Induction of CYP1A1 gene expression in H4‐II‐E rat hepatoma cells by benzo[e]pyrene

Abstract

In the rat, expression of the CYP1A1 gene is closely associated with arylhydrocarbon hydroxylase (AHH) enzyme activity. AHH is an inducile enzyme activity known to play an important role in the bioactivation of polycyclic aromatic hydrocarbons (PAHs) to mutagenic and carcinogenic metabolites. PAH-induced expression of the CYP1A1 gene appears to be regulated by several trans-acting factors, including the Ah receptor and the 4S PAH-binding protein. In this study, we used the PAH isomers benzo[a]pyrene (BaP) and benzo[e]pyrene (BeP) to further evaluate the role of the 4S PAH-binding protein in induction of the CYP1A1 gene in H4-II-E rat hepatoma cells. Although BaP is believed to bind to both the Ah receptor and the 4S protein, BeP has been reported to bind exclusively to the 4S protein. The results of the study presented here indicate that BaP and BeP induce the expression of the CYP1A1 gene, as measured by ethoxyresorufin O-deethylase (EROD) activity, in a concentration-dependent manner. However, BaP is about 25 times as potent as BeP in inducing EROD activity in these cells. Slot-blot analysis of total RNA isolated from these cells indicated that BeP, BaP, and 3-methylcholanthrene increased the level of CYP1A1 mRNA expression. Sucrose-gradient analysis of BeP binding activity indicated that BeP bound with high affinity to the 4S PAH-binding protein, but not to the Ah receptor. These results suggest that the 4S protein may play a role in the PAH-induced expression of the CYP1A1 gene in rat H4-II-E cells.

Ability of Polycyclic Aromatic Hydrocarbons to Induce 7-Ethoxyresorufin-o-deethylase Activity in a Trout Liver Cell Line

“…In mammalian cell lines the potency of PAHs as inducers of P4501A also has been found to decline as exposure time was lengthened. In H4IIE, a 72-h exposure to BaP did not result in EROD induction (Piskorska-Pliszczynska et al, 1986) but a 24-h one did (Houser et al, 1992). The EC s for the induction of AHH activity by BA in Hepa-1 cells and in human MCF-7 cells were approximately seven-fold higher at 24 h than at 6 h (Jaiswal et al, 1985).…”

The potent protective effect of wild ginseng (Panax ginseng C.A. Meyer) against benzo[α]pyrene-induced toxicity through metabolic regulation of CYP1A1 and GSTs

“…BP is primarily bioactivated by the catalysis of CYP1A1 (Huang et al, 1999). Furthermore, BP can induce expression of CYP1A1 via the aryl hydrocarbon receptor (Houser et al, 1992;Huang et al, 1999). We immunohistochemically examined the extent of CYP1A1 expression in rat liver Rats were treated as described in Table 1.…”

Evaluation of CYP1A Protein Induction, Biotransformation Capacity and DNA Adduct Formation in a Rat Hepatoma Cell Line (Fao), as Biomarkers of Organic Contamination in Environmental Soil Samples

“…We have previously shown a concentration-dependent increase in CYP1A protein content after exposure to environmentally relevant concentrations of B[a]P in Fao cells (Østby and Krøkje, 2002) (Figure 2 E). B[a]P is also a potent inducer of CYP1A in the rat hepatoma cell line H4IIE (Houser et al 1992) as well as in isolated hepatocytes from rat (Till et al 1999). Other PAH-compounds detected in the soil samples in the present study are also known CYP1A inducers in rat (Till et al, 1999).…”