ArticleToxicological sciences : an official journal of the Society of Toxicology2016
The Influence of Human Interindividual Variability on the Low-Dose Region of Dose-Response Curve Induced by 2,3,7,8-Tetrachlorodibenzo-p-Dioxin in Primary B Cells.
Article in Toxicological sciences : an official journal of the Society of Toxicology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
15 citing papers in PubMed, 17 citations in OpenAlex.
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- The aryl hydrocarbon receptor differentially modulates the expression profile of antibody isotypes in a human B-cell line.Toxicological sciences : an official journal of the Society of Toxicology · 2024Article
- Evolutive emergence and divergence of an Ig regulatory node: An environmental sensor getting cues from the aryl hydrocarbon receptor?Frontiers in immunology · 2023Review
- Genetics-Based Approach to Identify Novel Genes Regulated by the Aryl Hydrocarbon Receptor in Mouse Liver.Toxicological sciences : an official journal of the Society of Toxicology · 2021Article
- Identification of a Sensitive Human Immunological Target of Aryl Hydrocarbon Receptor Activation: CD5Frontiers in immunology · 2021Article
- Aryl hydrocarbon receptor-induced activation of the human IGH hs1.2 enhancer: Mutational analysis of putative regulatory binding motifs.Molecular immunology · 2020Article
- An Automated Method To Predict Mouse Gene and Protein Sequences Using Variant Data.G3 (Bethesda, Md.) · 2020Article
- TCDD-mediated suppression of naïve human B cell IgM secretion involves aryl hydrocarbon receptor-mediated reduction in STAT3 serine 727 phosphorylation and is restored by interferon-γ.Cellular signalling · 2020Article
- Characterizing Serpinb2 as a Modulator of TCDD-Induced Suppression of the B Cell.Chemical research in toxicology · 2018Article
- Lymphocyte-Specific Protein Tyrosine Kinase (LCK) is Involved in the Aryl Hydrocarbon Receptor-Mediated Impairment of Immunoglobulin Secretion in Human Primary B Cells.Toxicological sciences : an official journal of the Society of Toxicology · 2018Article
- Incorporating population-level genetic variability within laboratory models in toxicology: From the individual to the population.Toxicology · 2018Review
- Toxicodynamics of Mycotoxins in the Framework of Food Risk Assessment-An In Silico Perspective.Toxins · 2018Review
- Bridging the Data Gap FromFrontiers in public health · 2018Review
- A tiered approach to population-based in vitro testing for cardiotoxicity: Balancing estimates of potency and variability.Journal of pharmacological and toxicological methodsArticle
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
The influence of interindividual variability is not typically assessed in traditional toxicological studies. Given that chemical exposures occur in heterogeneous populations, this knowledge gap has the potential to cause undue harm within the realms of public health and industrial and municipal finances. A recent report from the National Research Council (NRC) suggests that when accounting for interindividual variation in responses, traditionally assumed nonlinear dose-response relationships (DRRs) for noncancer-causing endpoints would better be explained with a linear relationship within the low-dose region. To address this knowledge gap and directly test the NRC's assumption, this study focused on assessing the DRR between 2,3,7,8-tetracholorodibenzo-p-dioxin (TCDD) exposure and immune suppression in a cohort of unique human donors. Human B cells were isolated from 51 individual donors and treated with logarithmically increasing concentrations of TCDD (0-30 nM TCDD). Two endpoints sensitive to TCDD were assessed: (1) number of IgM-secreting B cells and (2) quantity of IgM secreted. The results show that TCDD significantly suppressed both the number of IgM-secreting B cells and the quantity of IgM secreted (P < .05). Statistical model comparisons indicate that the low-dose region of the two DRRs is best explained with a nonlinear relationship. Rather than assuming low-dose linearity for all noncancer-causing DRRs, our study suggests the need to consider the specific mode of action of toxicants and pharmaceuticals during risk-management decision making.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.