Exposure to 3,3′,4,4′,5‐pentachlorobiphenyl during embryonic development has a minimal effect on the cytochrome P4501A response to 2,3,7,8‐tetrachlorodibenzo‐<i>P</i>‐dioxin in cultured chicken embryo hepatocytes

Self Cite

Concentration-dependent effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), 2,3,4,7,8-pentachlorodibenzofuran (PeCDF), and 2,3,7,8-tetrachlorodibenzofuran (TCDF) on cytochrome P4501A (CYP1A) induction were determined in primary cultures of embryonic herring gull (Larus argentatus) hepatocytes exposed for 24 h. Based on the concentration that induced 50% of the maximal response (EC50), the relative potencies of TCDD and TCDF did not differ by more than 3.5-fold. However, also based on the EC50, PeCDF was 40-fold, 21-fold, and 9.8-fold more potent for inducing ethoxyresorufin-O-deethylase (EROD) activity, CYP1A4 mRNA expression, and CYP1A5 mRNA expression than TCDD, respectively. The relative CYP1A-inducing potencies of PeCDF and of other dioxin-like chemicals (DLCs) in herring gull hepatocytes (HEH RePs), along with data on concentrations of DLCs in Great Lakes herring gull eggs, were used to calculate World Health Organization toxic equivalent (WHO-TEQ) concentrations and herring gull embryonic hepatocyte toxic equivalent (HEH-TEQ) concentrations. The analysis indicated that, when using avian toxic equivalency factors (TEFs) recommended by the WHO, the relative contribution of TCDD (1.1-10.2%) to total WHO-TEQ concentration was higher than that of PeCDF (1.7-2.9%). These results differ from the relative contribution of TCDD and PeCDF when HEH RePs were used; PeCDF was a major contributor (36.5-52.9%) to total HEH-TEQ concentrations, whereas the contribution by TCDD (1.2-10.3%) was less than that of PeCDF. The WHO TEFs for avian species were largely derived from studies with the domestic chicken (Gallus gallus domesticus). The findings of the present study suggest that it is necessary to determine the relative potencies of DLCs in wild birds and to re-evaluate their relative contributions to the biochemical and toxic effects previously reported in herring gulls and other avian species.

Section: Source Of Eggs and Incubation Conditionsmentioning

confidence: 99%

2,3,4,7,8‐pentachlorodibenzofuran is a more potent cytochrome P4501A inducer than 2,3,7,8‐tetrachlorodibenzo‐p‐dioxin in herring gull hepatocyte cultures

Hervé

Crump

McLaren

et al. 2010

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“…Embryos were euthanized by decapitation, and hepatocytes were prepared by collagenase digestion and filtration, as described previously (Kennedy et al 1995;Head et al 2006). Embryos were euthanized by decapitation, and hepatocytes were prepared by collagenase digestion and filtration, as described previously (Kennedy et al 1995;Head et al 2006).…”

Section: Preparation and Dosing Of Cehsmentioning

confidence: 99%

A rapid method of preparing complex organohalogen extracts from avian eggs: Applications to in vitro toxicogenomics screening

Crump

Williams

Chiu

et al. 2019

Double‐crested cormorants are piscivorous birds that breed in variably contaminated colonies across the Laurentian Great Lakes of North America. Collection and preparation of environmentally relevant extracts from eggs that contain variable concentrations of organohalogen contaminants represents a minimally invasive approach to characterize potential effects of exposure using in vitro bioassays. In the present study, a rapid, efficient lipid freeze‐filtration extraction method was used to prepare extracts from double‐crested cormorant eggs collected from 5 breeding colonies that had variable organohalogen contaminant burdens. Extracts, solubilized in dimethyl sulfoxide, were administered to chicken embryonic hepatocytes (CEHs) to determine effects on cell viability, 7‐ethoxyresorufin‐O‐deethylase (EROD) activity, and messenger RNA expression using a chicken ToxChip polymerase chain reaction (PCR) array. The EROD median effect concentration (EC50) values were lower for extracts with greater organohalogen contaminant burdens and thus permitted an initial ranking of colonies based on the efficacy of eliciting an aryl hydrocarbon receptor–mediated response. The ToxChip PCR array data provided a more exhaustive, pathway‐based evaluation of extract effects; variability in the transcriptomic profiles was associated with organohalogen contaminant burdens. For example, extracts from Mud Island (Detroit River, MI, USA) had among the highest organohalogen contaminant burdens and elicited a greater biochemical (EROD EC50 = 0.005) and transcriptomic response (22/43 genes altered on the array) in CEHs compared with the least contaminated site, which was Mandarte Island (BC, Canada; EROD EC50 = 0.172; 8/43 genes altered). Avian eggs represent a useful biomonitoring tool for determining complex mixture effects, and the combination of a rapid extraction method, an in vitro bioassay, and targeted endpoint evaluation (biochemical and transcriptomic) shows great promise as an environmental effects monitoring approach. Environ Toxicol Chem 2019;38:811–819. © 2019 Crown in the right of Canada. Published by Wiley Periodicals Inc. on behalf of SETAC.

“…To further characterize the transcriptomic alterations of cytochrome P450 family 1 subfamily A member 4 (Cyp1a4) following PCR array analysis, the EROD assay was conducted in CEHs for one OFR that elicited the greatest Cyp1A4 mRNA induction, OFR7 (concentration range, 0.1-300 mM; Supplemental Data, Table S3), based on methods described in detail previously (Kennedy et al 1995;Head et al 2006). Plates were analyzed for EROD activity and total protein concentration using a Beckman Coulter DTX880 multimode detector.…”

Section: Erod Activitymentioning

confidence: 99%

Prioritization of 10 organic flame retardants using an avian hepatocyte toxicogenomic assay

Pagé-Larivière

Chiu

Jones

et al. 2018

As the number of chemicals developed and used by industry increases, the inherent limitations of traditional toxicology approaches become an unavoidable issue. To help meet the demand for toxicity evaluation, new methods, such as high-throughput toxicity screening, are currently being developed to permit rapid determination of toxic, molecular, and/or biochemical effects of a wide range of chemicals. In the present study, we demonstrate the utility of an avian in vitro toxicogenomics screening approach to determine the cytotoxic and transcriptomic effects of 10 organic flame retardants (OFRs) currently of international priority for ecological risk evaluation to prioritize and inform future toxicological studies. Hepatocytes from 2 avian species, chicken and double-crested cormorant, were prepared and exposed for 24 h to various concentrations (0-300 μM) of the following 10 OFRs: Chemical Abstracts Service registration numbers 29761-21-5, 56803-37-3 (p-tert-butylphenyl diphenyl phosphate [BPDP]), 65652-41-7, 68937-41-7 (phenol, isopropylated, phosphate [3:1] [IPPP]), 95906-11-9, 19186-97-1, 26040-51-7, 35948-25-5, 21850-44-2, and 25713-60-4. Cell viability, the 7-ethoxyresorufin-O-deethylase assay, and transcriptomic analysis using species-specific ToxChip polymerase chain reaction arrays were performed to evaluate the in vitro effect of these OFRs. Of the 10 OFRs assessed, BPDP and IPPP elicited the strongest cytotoxic and transcriptomic responses in both chicken and double-crested cormorant hepatocytes and are therefore recommended as priority candidates for further wildlife toxicological investigations. Environ Toxicol Chem 2018;37:3134-3144. © 2018 Crown in the right of Canada. Published by Wiley Periodicals Inc. on behalf of SETAC.