Inhibition of ethoxyresorufin-O-deethylase (EROD) activity in mixtures of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and polychlorinated biphenyls (PCBs)
Conference
·
OSTI ID:191267
- Univ. of Umeaa (Sweden). Inst. of Environmental Chemistry
- Univ. of Utrecht (Netherlands). Research Inst. of Toxicology
In the chicken liver, both cytochrome P450 1A1 and 1A2 have been found to be inducible by TCDD and other ``dioxin-like`` compounds. Induced cytochrome P450 1A1/2 monooxygenase activity is also suggested to affect the regulation of heme biosynthesis and to result in an increase of liver uroporphyrins, as well as other forms of porphyrins. 2,3,7,8-TCDD, 2,2{prime},4,6,6{prime}-PeCB (PCB{number_sign}104), and 2,2{prime},4,4{prime},5,5{prime}-HxCB (PCB{number_sign}153) were dosed to primary chicken embryo hepatocytes and effects on EROD activities and porphyrin accumulation were measured. Among the three compounds, only TCDD elicit measurable catalytic EROD activity (EC{sub 50} at 0.01 nM). However, all three compounds showed increased porphyrin concentrations at doses higher than 1 nM, 100 nM, and 50 nM, respectively. In the dose range, the porphyrin accumulation concur with a decrease in EROD activity. In order to study possible interaction between the two classes of compounds, chicken hepatocytes were dosed with mixtures of TCDD and PCB{number_sign}104 and PCB{number_sign}153, respectively. The combination of TCDD and the ortho-substituted PCBs (at doses which cause porphyrin accumulation) have an inhibitory effect on TCDD-induced EROD activity. The results support that there are nonadditive interactions between different classes of polyaromatic compounds, such as TCDD and ortho-substituted PCBs. The inhibition of the EROD activity could lead to a change in the dose-response curve, thereby influencing the EC{sub 50}-value, and thus great care should be taken when using EROD activity as a sum parameter for dioxin-like activity of complex environmental mixtures.
- OSTI ID:
- 191267
- Report Number(s):
- CONF-9511137--; ISBN 1-880611-03-1
- Country of Publication:
- United States
- Language:
- English
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