Interactions among Ah receptor agonists in a novel human bioassay for induction of cytochrome P-450 IA1
- Univ. of Windsor, Ontario (Canada). Great Lakes Inst. for Environmental Research
- Department of Fisheries and Oceans, Burlington, Ontario (Canada). Canada Centre for Inland Waters
A widespread technique for monitoring pollutant exposure and toxicity is based upon induction of the cytochrome P450 (CYP) enzyme system. Numerous classes of xenobiotics, including PCBs, PAHs, PCDDs and PCDFs, stimulate induction of the CYP IA1 subfamily via binding to the intracellular Ah receptor. A widely-used catalytic marker for this subfamily is ethoxyresorufin 0-deethylase (EROD). Toxic equivalency factors may be calculated for ranking toxicity of pollutants relative to agonists such as 2,3,7,8,-TCDD, a highly potent inducer and Ah receptor ligand. These methods typically utilize cell lines from rodents (e.g., H4IIE) or fish (e.g., RTL 149), and although such models may be relevant to these and related species, they are of little direct applicability to human health concerns. The laboratory has recently developed a system for monitoring EROD induction in the HepG2 human hepatoma cell line. Treatment of HepG2 cells with Ah receptor agonists such as TCDD elicits induction responses, comparable to those observed in non-human bioassays. When cells are exposed to TCDD and purified PCBs simultaneously, significant interactions are observed. Both inductive and non-inductive PCB congeners appear to inhibit TCDD-mediated EROD induction, presumably due to competition for the Ah receptor ligand-binding site. This may potentially lead to gross underestimation of the toxicity of complex mixtures in which such interactions take place. Results demonstrate the utility of this novel bioassay for assessing hazard of environmental pollutant mixtures to human as well as ecosystem health.
- OSTI ID:
- 398216
- Report Number(s):
- CONF-9511137-; ISBN 1-880611-03-1; TRN: IM9649%%424
- Resource Relation:
- Conference: 2. Society of Environmental Toxicology and Chemistry (SETAC) world conference, Vancouver (Canada), 5-9 Nov 1995; Other Information: PBD: 1995; Related Information: Is Part Of Second SETAC world congress (16. annual meeting): Abstract book. Global environmental protection: Science, politics, and common sense; PB: 378 p.
- Country of Publication:
- United States
- Language:
- English
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