Structure-Dependent Induction of CYP1A by Polychlorinated Biphenyls in Hepatocytes of Cynomolgus Monkeys (Macaca fascicularis)

Burght, Aafje S.A.M. van der; Clijsters, P. J.; Horbach, G. Jean; Andersson, Patrik L.; Tysklind, Mats; Berg, Martin van den

doi:10.1006/taap.1998.8606

Cited by 24 publications

(11 citation statements)

References 46 publications

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“… a Determined by van der Burght et al [9–11]. EC50 values (μM) and Y max (% relative to PCB 169) are shown. …”

Section: Resultsmentioning

confidence: 99%

“…Recently, cytochrome P4501A (CYP1A) activity induced by exposure to PCBs has been measured for intact hepatocytes from cynomolgus monkeys ( Macaca fascicularis ) [9], male castrated pigs (Great Yorkshire × Dutch Landrace) [10], and chicken embryos (White Leghorn) [11]. The induction was measured for 20 PCBs, which were selected to represent all 154 tetra‐ to hepta‐chlorinated congeners, by applying factorial design in combination with principal component analysis (PCA) [12].…”

Section: Introductionmentioning

confidence: 99%

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Multivariate modeling of polychlorinated biphenyl–induced CYP1A activity in hepatocytes from three different species: Ranking scales and species differences

Andersson

Burght

Berg

et al. 2000

Enviro Toxic and Chemistry

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Cytochrome P4501A–induced activity of 20 selected polychlorinated biphenyls (PCBs) was evaluated by measuring ethoxyresorufin‐O‐deethylase and methoxyresorufin‐O‐demethylase activities induced in the hepatocytes of cynomolgus monkeys, male castrated pigs, and chicken embryos. Quantitative structure‐activity relationships have been established, including 52 physi‐cochemical parameters and different measures of the dose‐response curves. Relative effect potencies are predicted for the 154 tetra‐to hepta‐PCBs and reported for the most potent congeners according to both EC50 and maximal response values. Important physicochemical parameters of the PCBs as related to the modeled activity are parts of their ultraviolet absorption spectra, the Henry's law constant, the ionization potential, and the octanol‐water partition coefficient. Interspecies differences were found in terms of varied sensitivity to different structural subgroups of the compounds. The chicken hepatocyte assay showed the most specific structure‐activity relationship, with high activity for the non‐ortho PCBs, whereas the pig hepatocytes responded even for some di‐ to tetra‐ortho PCBs. An interspecies response, the principal induction potency, is presented for the 41 most potent PCBs. These responses showed strong correlation with the toxic equivalency factors and are likely to be useful in risk assessment of the compounds.

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“… a Determined by van der Burght et al [9–11]. EC50 values (μM) and Y max (% relative to PCB 169) are shown. …”

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Multivariate modeling of polychlorinated biphenyl–induced CYP1A activity in hepatocytes from three different species: Ranking scales and species differences

Andersson

Burght

Berg

et al. 2000

Enviro Toxic and Chemistry

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“…1). This compound shows dioxin-like activity and activates the aryl hydrocarbon receptor (AhR) pathway (van der Burght et al, 1999). BDE47 and PCB153 were clustered in a separate branch of the dendrogram, indicating that the gene expression profiles induced by these chemicals are more alike compared with the other exposures.…”

Section: Discussionmentioning

confidence: 99%

“…Molecular biology tools such as gene expression analysis are instrumental for a better understanding of receptor signaling and biological pathways that are triggered by these EDCs. For example, PCB126 is a known aryl hydrocarbon receptor (AhR) ligand that causes cytochrome P450 (CYP)1A induction and shows antiestrogenic activity (Boelsterli, 2007;Den Hond and Schoeters, 2006;van der Burght et al, 1999). Other EDCs have estrogenic (PCB153, BPA) or (anti)androgenic (BDE47) activities.…”

Section: Introductionmentioning

confidence: 98%

Cultured human peripheral blood mononuclear cells alter their gene expression when challenged with endocrine-disrupting chemicals

et al. 2013

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“…A study in rat hepatocytes found that mono-ortho PCBs are primarily metabolized by CYP1A and primarily induce CYP1A (with CYP2B being induced to a lesser extent) [27]. CYP1A induction by PCB 118 has also been shown to be orders of magnitude greater than induction by multi-ortho PCBs [28]. Meanwhile, CYP2B induction from both PCB 118 and multi-ortho PCBs was the same order of magnitude [25].…”

Section: Methodsmentioning

confidence: 99%

Bayesian Analysis of a Lipid-Based Physiologically Based Toxicokinetic Model for a Mixture of PCBs in Rats

Sasso

Georgopoulos

Isukapalli

et al. 2012

Journal of Toxicology

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A lipid-based physiologically based toxicokinetic (PBTK) model has been developed for a mixture of six polychlorinated biphenyls (PCBs) in rats. The aim of this study was to apply population Bayesian analysis to a lipid PBTK model, while incorporating an internal exposure-response model linking enzyme induction and metabolic rate. Lipid-based physiologically based toxicokinetic models are a subset of PBTK models that can simulate concentrations of highly lipophilic compounds in tissue lipids, without the need for partition coefficients. A hierarchical treatment of population metabolic parameters and a CYP450 induction model were incorporated into the lipid-based PBTK framework, and Markov-Chain Monte Carlo was applied to in vivo data. A mass balance of CYP1A and CYP2B in the liver was necessary to model PCB metabolism at high doses. The linked PBTK/induction model remained on a lipid basis and was capable of modeling PCB concentrations in multiple tissues for all dose levels and dose profiles.

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Structure-Dependent Induction of CYP1A by Polychlorinated Biphenyls in Hepatocytes of Cynomolgus Monkeys (Macaca fascicularis)

Cited by 24 publications

References 46 publications

Multivariate modeling of polychlorinated biphenyl–induced CYP1A activity in hepatocytes from three different species: Ranking scales and species differences

Multivariate modeling of polychlorinated biphenyl–induced CYP1A activity in hepatocytes from three different species: Ranking scales and species differences

Cultured human peripheral blood mononuclear cells alter their gene expression when challenged with endocrine-disrupting chemicals

Bayesian Analysis of a Lipid-Based Physiologically Based Toxicokinetic Model for a Mixture of PCBs in Rats

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