Different In Vitro Systems Affect CYPIA1 Activity in Response to 2,3,7,8-Tetrachlorodibenzo-p-dioxin

Toxicology in Vitro : an International Journal Published in Association with BIBRA
N A Mufti, M L Shuler

Abstract

The induction of cytochrome P450IA1 (CYP1A1) activity in human hepatoma cell lines has been used as a model response for exposure to the environmental contaminant, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). CYP1A1 induction is mediated by the intracellular Ah receptor. We have designed a cell culture analogue system to evaluate the effect of low dose continuous exposures to TCDD such that the responses can be compared with traditional static in vitro exposures. The two-compartment model is designed to mimic aspects of time-dependent dose exposure in humans and consists of a 'liver' compartment with HepG2 cells and an 'other tissues' compartment. Exposure of microcarrier-attached HepG2 cells in spinner flask to a single dose of TCDD resulted in an EC(50) for ethoxyresorufin-o-deethylase (EROD) activity induction of 1.49nm. Using a one-compartment reactor with continuous TCDD dosing resulted in an EC(50) for EROD induction of 0.69nm TCDD. Finally, using a two-compartment reactor with continuous TCDD dosing resulted in an EC(50) for EROD induction of about 0.05nm. Parallel studies using (3)H-TCDD were performed to determine the amount of cell associated (3)H-TCDD and subsequently to estimate the amount of bound Ah receptor. CYPIA...Continue Reading

References

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Citations

Mar 27, 2003·Pediatric and Developmental Pathology : the Official Journal of the Society for Pediatric Pathology and the Paediatric Pathology Society·Maria ParizhskayaKareem Abu-Elmagd

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