| 1. |
- Andersson, Patrik, et al.
(författare)
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Multivariate modeling of polychlorinated biphenyl-induced CYP1A activity in hepatocytes from three different species : ranking scales and species differences
- 2000
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Ingår i: Environmental Toxicology and Chemistry. - : Wiley. - 0730-7268 .- 1552-8618. ; 19:5, s. 1454-1463
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Tidskriftsartikel (refereegranskat)abstract
- 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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| 2. |
- Van der Burght, A S A M, et al.
(författare)
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Structure dependent induction of CYP1A by polychlorinated biphenyls in hepatocytes of male castrated pigs
- 2000
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Ingår i: Chemosphere. ; 41:10, s. 1697-1708
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Tidskriftsartikel (refereegranskat)abstract
- Hepatocytes cultures prepared from castrated pig hepatocytes (Great YorkshirexDutch Landrace), as a model for human liver, were used to study the effect of twenty polychlorinated biphenyls (PCBs) on CYP1A activity, measured as the dealkylation of either ethoxyresorufin or methoxyresorufin. The selection of the PCBs was based on their differences in physico-chemical properties. The non-ortho and mono-ortho substituted PCBs were the most potent CYP1A inducers in pig hepatocytes. In addition, several multiple-ortho substituted congeners, with five or more chlorine atoms, were inducers of CYP1A activity as well. Their relative effect potencies (REP) were proximately 10,000 times lower than the most potent congener, 3,3',4,4',5 PeCB (PCB#126). Using partial least-squares (PLS) modeling, predictions of CYP1A activity could be made for all tetra to hepta substituted congeners. Several multiple-ortho substituted PCBs, which are highly abundant in the biotic and abiotic environment, have been found to induce CYP1A activity in pig hepatocytes. Because induction of CYP1A activity is used as biomarker for Ah-receptor mediated responses, it is suggested to include these congeners in future risk assessment.
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| 3. |
- Voiea, Ø A, et al.
(författare)
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Activation of Respiratory Burst in Human Granulocytes by Polychlorinated Biphenyls : A Structure–Activity Study
- 2000
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Ingår i: Toxicology and Applied Pharmacology. - : Elsevier BV. - 0041-008X. ; 167:2, s. 118-24
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Tidskriftsartikel (refereegranskat)abstract
- The respiratory burst in human granulocytes activated by 33 different congeners of polychlorinated biphenyls (PCBs) was measured as luminol-amplified chemoluminescence. The selection of 20 (training set) compounds was based on multivariate chemical characterization, laying the groundwork for covering the whole chemical series of tetra- through hepta-chlorinated PCBs. In addition 6 congeners were used as a validation set, and 7 were mono- to tri-chlorinated congeners representing low-chlorinated compounds not covered by the training set. Only ortho-substituted biphenyls activate respiratory burst. There is a correlation between activated respiratory burst and the total surface area of congeners up to 230 × 10−20 m2. Congeners of larger size show a reduced activity. There is also a correlation between respiratory burst activity and the number of ortho-substituents. Furthermore, there is also a correlation with parameters that describe absolute hardness of the molecule and respiratory burst activity. Congeners with a 2,4,6-substitution on one biphenyl ring are optimal activators. In conclusion, all three factors, size, rotation, and electronic properties, which are not independent of each other, are important for the activity of the PCBs.
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| 4. |
- Westerlund, L, et al.
(författare)
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Early life-stage mortality in zebrafish (Danio rerio) following maternal exposure to polychlorinated biphenyls and estrogen
- 2000
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Ingår i: Environmental Toxicology and Chemistry. - 0730-7268. ; 19:6, s. 1582-8
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Tidskriftsartikel (refereegranskat)abstract
- In the present study, specific polychlorinated biphenyl (PCB) congeners were examined far embryo and early life stage mortality in zebrafish (Danio rerio). A set of eight PCBs and two hydroxylated PCBs and 17 beta-estradiol were tested. Of the compounds tested, 4'-OH-PCB30 (hydroxylated polychlorinated biphenyl) and PCB 104 were found to be highly toxic to embryos following maternal exposure and transfer to the oocyte. It was also observed that 17 beta-estradiol exposure resulted in a high incidence of embryo mortality. Analysis of estrogen receptor levels during embryonic development showed increased mRNA (ribonucleic acid) levels from the 1K stage to 50% epiboly. Following injection of the different compounds, the estrogen receptor mRNA levels were also analyzed in adult male fish to determine if there was a correlation between embryo mortality and estrogenicity of the studied PCBs. The two PCBs that were highly embryo toxic were observed to be estrogenic.
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| 5. |
- Åkerblom, N, et al.
(författare)
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Impact of Polychlorinated Naphthalenes (PCNs) in Juvenile Baltic Salmon, Salmo salar: Evaluation of Estrogenic Effects, Development, and CYP1A Induction
- 2000
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Ingår i: Archives of Environmental Contamination and Toxicology. - : Springer Science and Business Media LLC. - 0090-4341 .- 1432-0703. ; 38:2, s. 225-33
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Tidskriftsartikel (refereegranskat)abstract
- Juvenile Baltic salmon, Salmo salar, were fed commercial salmon food contaminated with different concentrations of polychlorinated naphthalenes (PCNs; 0.1, 1, 2, or 10 μg PCN/g food). Among other effects, possible estrogenic impact caused by PCNs were evaluated. Fish were therefore fed a diet contaminated with 17β-estradiol (E2; 0.94 or 9.4 μg E2/g food), as a positive control. After 8, 13, 17, and 41 weeks, sampling took place. Growth, liver somatic index (LSI), EROD activity, and vitellogenin content in blood plasma were measured along with morphological studies of gonads and chemical analyses to determine the effects caused by PCNs. Exposure to PCNs did not seem to have any effects on body weight gain, since the group fed the high dose followed the growth in the control group during the entirely experimental period. After 41 weeks of exposure the groups fed 2 and 10 μg PCN/g food had significantly lower LSIs compared with the control, indicating liver toxic effects of PCNs. Furthermore, a dose-dependent induction of EROD activity was found. At week 41, the control group had an activity of 4.9 ± 4.8 pmol/mg prot/min, whereas it was between 69 ± 21 and 720 ± 370 pmol/mg prot/min in the exposed groups, respectively. Examination of gonadal morphology showed that PCNs also had negative effects on ovaries in Baltic salmon, including delayed development. The distribution between females and males, gonadal morphology, and vitellogenin content in blood plasma did, however, indicate that PCNs are not capable of causing effects similar to E2 or xenoestrogens. Exposure to both of the concentrations of E2 resulted in decreased body weight gain, increased LSI, and feminization of the gonads. E2 did, however, not induce any EROD activity.
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