Structure dependent induction of CYP1A by polychlorinated biphenyls in hepatocytes of male castrated pigs

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

doi:10.1016/s0045-6535(00)00013-8

Cited by 14 publications

(11 citation statements)

References 48 publications

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“…1) There is evidence suggesting that the immune system is one of the most sensitive indicators of adverse PCB induced health effects. [2][3][4] PCBs and other HAHs mediate their various toxic effects through the aromatic hydrocarbon receptor (AhR), a ligand activated transcription factor.…”

mentioning

confidence: 99%

Expression of Cyclooxygenase-2 and Pro-inflammatory Cytokines Induced by 2,2',4,4',5,5'-Hexachlorobiphenyl (PCB 153) in Human Mast Cells Requires NF-.KAPPA.B Activation.

Kwon

Lee

Moon

et al. 2002

Biological & Pharmaceutical Bulletin

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Mast cells are critical for initiating innate immune and inflammatory responses by releasing a number of pro-inflammatory mediators. The potential immunomodulatory properties of hydrogenated aromatic hydrocarbons have been the subject of extensive investigation, as the immune system is a sensitive target for hydrogenated aromatic hydrocarbon toxicity. In this report, the effects of polychlorinated biphenyl (PCB) on the expression of cyclooxygenase-2 and pro-inflammatory cytokines such as interleukin-1b b (IL-1b b), IL-6 and tumor necrosis factor (TNF)-a a in the human leukemic mast cell line were investigated. TNF-a a and IL-1b b expressed their respective mRNA in the presence or absence of PCB, while cyclooxygenase-2 (COX-2) and IL-6 mRNA expression were highly induced by PCB after 2 h. Moreover, pre-treatment with the nuclear factor (NF)-k kB pathway inhibitor, pyrrolidine dithiocarbamate, suppressed COX-2, TNF-a a and IL-1b b induction and reduced the IL-6 mRNA levels induced by PCB. The NF-k kB activity was determined by electrophoretic mobility shift analysis (EMSA) using an oligonucleotide containing a consensus NF-k kB binding sequence. Stimulating the cells with PCB activated NFk kB. However, pre-treating them with a NF-k kB pathway inhibitor, pyrrolidine dithiocarbamate, suppressed PCBinduced NF-k kB activation. This suggests that PCB induces cycloxoygenase-2 and pro-inflammatory cytokine expression, and that this induction occurs through NF-k kB.

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confidence: 99%

Expression of Cyclooxygenase-2 and Pro-inflammatory Cytokines Induced by 2,2',4,4',5,5'-Hexachlorobiphenyl (PCB 153) in Human Mast Cells Requires NF-.KAPPA.B Activation.

Kwon

Lee

Moon

et al. 2002

Biological & Pharmaceutical Bulletin

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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%

“…Relative effect potencies values were calculated for all 154 tetra‐ to hepta‐chlorinated biphenyls, in which PCB126 was set to REP = 1 (for details, see van der Burght et al [9–11]). The congeners were classified according to their REP ratings in the following five groups: REP ≥ 0.01, 0.01 > REP ≥ 0.001, 0.001 > REP ≥ 0.0001, 0.0001 > REP ≥ 0.00001, and no CYP1A induction.…”

Section: Resultsmentioning

confidence: 99%

“…Further, CYP1A1 is probably induced in monkey hepatocytes after exposure to different PCBs [35]. The cytochrome P450 system of the pig is the least known; consequently, the pig isoforms involved here have not yet been identified [10].…”

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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Alterations in geometry, biomechanics, and mineral composition of juvenile rat femur induced by nonplanar PCB‐155 and/or planar PCB‐169

Brankovič

Jovanovski

Jevnikar

et al. 2016

Environmental Toxicology

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Exposure to widespread lipophilic and bioaccumulative polychlorinated biphenyls (PCBs) induces diverse biochemical and toxicological responses in various organs, including the bone. The aim of this study was to evaluate the changes in growth rate, geometry, serum, and bone biochemical parameters and biomechanics of juvenile rat femur induced by lactational exposure to nonplanar PCB-155 and planar PCB-169 individually and in combination. Fifteen lactating Wistar rats were divided into four groups (PCB-169, PCB-155, PCB-155+169, and control), and PCBs were administered intraperitoneally at different time points after delivery. Femurs from 22-day-old offspring were analyzed by microCT, three-point bending test and inductively coupled plasma-mass spectrometry (ICP-MS) to obtain data on bone geometry, biomechanics and mineral composition. The serum levels of calcium, phosphate and alkaline phosphatase were also determined. Lactational exposure to planar PCB-169 resulted in shorter and thinner femurs, reduced endosteal and periosteal perimeters, smaller total cross-sectional and medullary areas, and lowered serum bone marker levels and calcium levels in the bone, while femur mechanical properties were not significantly altered. The changes observed in the combination exposure (PCB-155+169) group were similar to those observed in the PCB-169 group but were less pronounced. In summary, our results demonstrate that alterations in lactationally exposed offspring were primarily induced by planar PCB-169. The milder outcome in the combined group suggested that the PCB-169-mediated toxic effects on the bone might be reduced by a nonplanar PCB-155 congener. © 2016 Wiley Periodicals, Inc. Environ Toxicol 32: 1135-1146, 2017.

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Structure dependent induction of CYP1A by polychlorinated biphenyls in hepatocytes of male castrated pigs

Cited by 14 publications

References 48 publications

Expression of Cyclooxygenase-2 and Pro-inflammatory Cytokines Induced by 2,2',4,4',5,5'-Hexachlorobiphenyl (PCB 153) in Human Mast Cells Requires NF-.KAPPA.B Activation.

Expression of Cyclooxygenase-2 and Pro-inflammatory Cytokines Induced by 2,2',4,4',5,5'-Hexachlorobiphenyl (PCB 153) in Human Mast Cells Requires NF-.KAPPA.B Activation.

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

Alterations in geometry, biomechanics, and mineral composition of juvenile rat femur induced by nonplanar PCB‐155 and/or planar PCB‐169

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