Interindividual variation in the cytochrome P4501A response to 2,3,7,8‐tetrachlorodibenzo‐<i>p</i>‐dioxin in herring gull embryo hepatocytes

Head, Jessica; Kennedy, Sean W.

doi:10.1002/etc.4350

Cited by 6 publications

(3 citation statements)

References 50 publications

(86 reference statements)

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“…One possibility is that large interindividual differences in metabolic capacity for PAHs occurred but were not detectable because analytical determinations of BaP were performed on liver tissue pooled from 3 embryos. Previous studies have reported large levels of interindividual variation in induction levels of the enzymes that metabolize PAHs in avian embryos (Head and Kennedy ).…”

Section: Resultsmentioning

confidence: 99%

An Early–Life Stage Alternative Testing Strategy for Assessing the Impacts of Environmental Chemicals in Birds

Farhat

Crump

Bidinosti

et al. 2019

Enviro Toxic and Chemistry

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Early-life stage (ELS) toxicity tests are recognized as an advancement over current testing methodologies in terms of cost, animal use, and biological relevance. However, standardized ELS tests are not presently available for some vertebrate taxa, including birds. The present study describes a Japanese quail (Coturnix japonica) ELS test that is a promising candidate for standardization and applies it to test 8 environmental chemicals (ethinylestradiol, benzo[a]pyrene, chlorpyrifos, fluoxetine, lead(II)nitrate, trenbolone, seleno-L-methionine, hexabromocyclododecane). Individual chemicals were injected into the air cell of unincubated Japanese quail eggs at 3 concentrations, all predicted to cause ≤20% mortality. Survival to embryonic day 16 was consistently high (>90%) among the vehicle-injected controls. All chemicals, except ethinylestradiol, were detected in liver tissue, most at concentrations suggestive of embryonic clearance. Adverse effects were observed for 5 of the 8 chemicals; chlorpyrifos (41.1 µg/g) significantly increased developmental abnormalities and decreased embryo and gallbladder mass. Ethinylestradiol (54.2 µg/g) and hexabromocyclododecane (0.02 µg/g) decreased embryo mass and tarsus length, respectively. Benzo[a]pyrene (0.83 µg/g) and fluoxetine hydrochloride (32.7 µg/g) exceeded the 20% mortality cutoff. No effects were observed following lead(II)nitrate, seleno-L-methionine, or trenbolone exposure up to 10.7, 0.07, and 4.4 µg/g, respectively. Overall, our ELS approach was time-and cost-effective, caused minimal mortality in controls, effectively delivered diverse chemicals to the embryo, and permitted identification of apical outcomes, all of which provide support toward standardization.

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Section: Resultsmentioning

confidence: 99%

An Early–Life Stage Alternative Testing Strategy for Assessing the Impacts of Environmental Chemicals in Birds

Farhat

Crump

Bidinosti

et al. 2019

Enviro Toxic and Chemistry

Self Cite

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“…posure route/duration/frequency and toxicological susceptibility has been reported for humans based on factors including genetics, developmental stage, dietary pattern, and behavior . Variation in gene expression among individuals is also reported in avian species (Head & Kennedy, 2019). A recent study showed that the hepatic transcriptome was less variable in ELS than in adult Japanese quail (Legrand et al, 2022).…”

Section: Interindividual Variability Interindividual Variability In Ex-mentioning

confidence: 86%

Hepatic Transcriptomic Responses to Ethinylestradiol in Two Life Stages of Japanese Quail

Jeon

Crump

Boulanger

et al. 2022

Enviro Toxic and Chemistry

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Chemical risk assessment for avian species typically depends on information from toxicity tests performed in adult birds. Early-life stage (ELS) toxicity tests have been proposed as an alternative, but incorporation of these data into existing frameworks will require knowledge about the similarities/differences between ELS and adult responses. The present study uses transcriptomics to assess hepatic gene expression in ELS and adult Japanese quail following exposure to ethinylestradiol (EE2). Prior to incubation, ELS quail were dosed with measured EE2 concentrations of 0.54, 6.3, and 54.2 µg/g egg weight via air cell injection. Adult quail were fed a single dose of EE2 at nominal concentrations of 0, 0.5, and 5 mg/kg body weight by gavage. Liver tissue was collected from five to six individuals per dose group at mid-incubation for ELS quail and 4 days after dosing for adults. A total of 283 and 111 differentially expressed genes (DEGs) were detected in ELS and adult quail, respectively, 16 of which were shared across life stages. Shared DEGs included estrogenic biomarkers such as vitellogenin genes and apovitellenin-1. For the dose groups that resulted in the highest number of DEGs (ELS, 6.3 µg/g; adult, 5 mg/kg), 21 and 35 Kyoto Encyclopedia of Genes and Genomes pathways were enriched, respectively. Ten of these pathways were shared between life stages, including pathways involved with signaling molecules and interaction and the endocrine system. Taken together, our results suggest conserved mechanisms of action following estrogenic exposure across two life stages, with evidence from differential expression of key biomarker genes and enriched pathways. The present study contributes to the development and evaluation of ELS tests and toxicogenomic approaches and highlights their combined potential for screening estrogenic chemicals.

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“…Interindividual variation in herring gull populations has been investigated in response to environmental TCDD contamination. 30 All 55 hepatocyte cultures varied in CYP1A4 expression in a concentration-dependent manner. CYP1A4 was confirmed to be the dominant isoform in the hepatocytes, and basal rates varied 20-fold for CYP1A4 and 126-fold for CYP1A5.…”

Section: Primary Cell Culturesmentioning

confidence: 99%

Ecotoxicology assessments in avian species using cell-based models: A review

Ball

Lavado

2021

Avian Biology Research

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Cell-based models in avian species have historically focused on virology due to the demands of animal agriculture and vaccine production industries. Recent years have witnessed a gradual rise in the use of these models ( in ovo, cell lines, primary cell cultures, organ slices, and organ-on-a-chip) in ecotoxicological studies as scientists and governments begin the shift to new approach methodologies, a shift validated by the recent memo by the Environmental Protection Agency announcing the end of mammalian testing in the next two decades. This rise has been hindered by the limited standards available for avian species and the unknowns surrounding cell-based assay applicability in extrapolation to in vivo. Toxicologists have incorporated these models in many different studies, including maternal deposition, mechanistic, metabolic, and non-target analysis methods, demonstrating the broad utility of cell-based assays. In ovo methods are ideal for reproductive and early life stage development studies, primary cell cultures for metabolic analysis, cell lines for long term studies requiring culture, organ slices for metabolic research, and organ-on-a-chip models for predictive analysis. These models all have their limitations that researchers need to consider when choosing which is most appropriate for the intended research, however. The current indications are that future avian cell-based model testing would benefit from expanding the species diversity available in cell lines and increasing metabolic conservation in full replacement methods. In ovo and primary cell culture methods should also be examined to increase efficiency and further reduce animal usage. This review examines the use, limitations, and published applications of these models in an ecotoxicological context to understand the current state of avian cell-based models to explain what future directions should be taken and how best to apply the methods available to current problems that avian researchers are approaching.

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Interindividual variation in the cytochrome P4501A response to 2,3,7,8‐tetrachlorodibenzo‐p‐dioxin in herring gull embryo hepatocytes

Cited by 6 publications

References 50 publications

An Early–Life Stage Alternative Testing Strategy for Assessing the Impacts of Environmental Chemicals in Birds

An Early–Life Stage Alternative Testing Strategy for Assessing the Impacts of Environmental Chemicals in Birds

Hepatic Transcriptomic Responses to Ethinylestradiol in Two Life Stages of Japanese Quail

Ecotoxicology assessments in avian species using cell-based models: A review

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