| 1. |
- Celander, Malin C., 1962, et al.
(författare)
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DEVELOPMENT OF ALTERNATIVE MATHEMATICAL TOOLS TO ASSESS SYNERGISTIC MIXTURE EFFECTS
- 2015
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Ingår i: 18th International symposium on Pollutant Responses in Marine Organisms (PRIMO18).
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Mixture effects are well known problems but chemical legislations are typically based on single chemical toxicity, which is unfortunate as chemicals occur as mixtures in the environment. There are mathematical models to assess additive mixture effects that are based on linear mixture effects such as toxicodynamic interactions. Chemicals with same or different mode-of-actions can also interfere with each other’s elimination pathways that can result in toxicokinetic interactions and cause indirect mixture effects. Therefore, chemicals that inhibit CYP enzymes in the elimination pathways of different classes of environmental pollutants can cause non-linear mixture effects that are more-than-additive. More-than-additive mixture effects have been observed between azoles and other classes of environmental pollutants such as estrogenic chemicals and aromatic hydrocarbons, as a result of toxicokinetic interactions via CYP1A/CYP3A inhibitions. There is need for new mathematical models to assess non-linear mixture effects. We have initiated the development of alternative mathematical tools to forecast non-linear mixture effects that are based on toxicokinetic interactions from earlier lab-studies in fish and fish cells. Time-dynamic is a key factor in toxicokinetic interactions and therefore we will combine multiple differential equations in the models. These equations describe how one chemical’s concentration changes over time in relationship to changes of another chemical’s concentration over time and how that affect biomarker responses such as CYP1A and vitellogenin. We will use statistical tools to quantitatively fit the suggested models with data from lab-studies. Non-linear models can be used to describe synergistic mixture effects. Those could be bottom-up-models, where we start from the different chemicals involved, or they could be top-down-models, where we fit a multi-dimension function to a given dataset using an auxiliary non-linear model. Our preliminary non-linear mathematical top-down model describes how the vitellogenin and the CYP1A biomarker responses can vary with concentrations of a synthetic estrogen and an antimycotic azole.
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| 2. |
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| 3. |
- Cholumpai, Varaporn, et al.
(författare)
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Accumulation and clearance of PAHs and CYP1A levels in farmed green mussels (Perna viridis L.) from a coastal industrial area in Thailand
- 2015
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Ingår i: EnvironmentAsia. - 1906-1714. ; 8:2, s. 109-117
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Tidskriftsartikel (refereegranskat)abstract
- Green mussels (Perna viridis L.) that inhabit along coastal areas with established petro-chemical industries are likely to be exposed to petroleum hydrocarbons. In year 2011, polycyclic aromatic hydrocarbons (PAHs) accumulated (i.e. total of 16 PAH congeners) in three different sizes of farmed mussels in the Maptaphut industrial estate which is an industrial park in the Gulf of Thailand. The levels of mean total PAHs (0.4303 ± 0.3067 µg/g dry weight) in large sized (consumable size) mussels were 16 and 8 times higher than medium and small sized mussels. Levels of total carcinogenic PAHs (0.0311 ± 0.0310 µg/g dry weight) in consumable size mussels were 15 and 11 times higher compared to medium and small sized mussels. Two carcinogenic PAHs (i.e. chrysene and benzo[a]anthracene) were detected in all sized mussels. The ratio of high molecular weight versus low molecular weight PAHs in all sized mussels indicated the presence of pyrogenic PAHs contamination over petrogenic PAHs in this coastal area. Further studies were carried out in year 2012 involved depuration in consumable sized mussels and effects on the cytochrome P450 1A (CYP1A) biomarker were analyzed over a 30 day depuration period. The half-life was five days for total PAH burden (0.4765 ± 0.0615 µg/g dry weight), which included four non-carcinogenic PAHs. After 10, 15 and 30 days depuration in clean water, the mean total PAHs levels decreased gradually but yet significantly (0.2501 ± 0.0186, 0.1350 ± 0.0122 and 0.1554 ± 0.0353 µg/g dry weight, respectively) compared to the PAH levels at day 0. Levels of CYP1A declined accordingly and at 30 days depuration CYP1A protein levels were significantly reduced by almost 3-fold compared the PAH levels in mussels from the Maptaphut industrial estate. The results show that farmed green mussels reared for human consumptions are exposed to PAHs including carcinogenic PAHs and that clearance of these PAHs is evident at 30 days depuration. This study demonstrates the importance of analysing PAHs in mussels and the usefulness of the CYP1A biomarker to assess exposures of PAHs in Thailand coastal waters. Therefore, a continuous monitoring and evaluation of PAHs contamination in marine species is a priority in this area and other petro-chemical estate areas of Thailand in order to reduce the risk of dietary exposures to carcinogenic PAHs from consumption of green mussels as well as to endorse reduced anthropogenic releases of PAHs into the marine ecosystem.
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| 4. |
- Gräns, Johanna, 1979, et al.
(författare)
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Mixture effects between different azoles and beta-naphthoflavone on the CYP1A biomarker in a fish cell line
- 2015
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Ingår i: Aquatic Toxicology. - : Elsevier BV. - 0166-445X. ; 164, s. 43-51
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Tidskriftsartikel (refereegranskat)abstract
- The cytochrome P450 1A (CYP1A) biomarker response was studied in the Poeciliopsis lucida hepatocellular carcinoma (PLHC-1) cell line, which represents a good model for studies on aryl hydrocarbon receptor (AhR) - CYP1A signaling. The PLHC-1 cells were exposed to the prototypical CYP1A inducer and AhR agonist β-naphthoflavone (BNF) in combination with different azoles. Two imidazoles (clotrimazole and prochloraz) and two benzimidazoles (nocodazole and omeprazole) were used. Exposure to clotrimazole, prochloraz and nocodazole resulted in 2-4 fold induction of the CYP1A mediated ethoxyresorufin-O-deethylase (EROD) activities at 24 and 48 hrs, whereas exposure to the omeprazole for 48 hrs had no effect on the EROD activity. Clotrimazole, nocodazole and prochloraz also acted as inhibitors of EROD activities in situ in PLHC-1 cells (IC50=1.3 – 7.7 µM), whereas omeprazole had no effect on this activity (IC50=72 µM). Exposure to 10 µM prochloraz resulted in 3-fold induction of CYP1A mRNA and exposure to 10 µM nocodazole resulted in 16-fold induction of CYP1A mRNA levels at 24 hrs compared to controls. In the mixture experiments, more-than-additive mixture effects between BNF and the azoles clotrimazole, prochloraz and nocodazole on EROD activities were evident, with nocodazole showing the strongest mixture effect. The presence of nocodazole increased the response to BNF up to 200-fold on CYP1A mRNA and up to 16-fold on EROD activities and prolonged the effect of BNF exposure on EROD activities by 24 hrs or longer. This suggests that azoles that are inhibitors and/or competing substrates for the CYP1A enzymes can cause increased sensitivity to exposures to chemicals that depend on CYP1A metabolism for their elimination in situations of mixed chemical exposures. The results also suggest that the EROD biomarker response can be significantly affected in azole-contaminated areas. The responsiveness of the EROD biomarker to BNF exposure was studied in PLHC-1 that had been pre-treated with nocodazole for 5 or 24 hrs at concentrations that are known to disassemble microtubules at 24 hrs in these cells. Pre-treatment of PLHC-1 cells with nocodazole for either 5 or 24 hrs had no effect on the responsiveness to BNF exposure, which implies that the EROD activity can be induced in cells with disassembled microtubules.
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| 5. |
- Gräns, Johanna, 1979, et al.
(författare)
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Regulation of pregnane-X-receptor, CYP3A and P-glycoprotein genes in the PCB-resistant killifish (Fundulus heteroclitus) population from New Bedford Harbor
- 2015
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Ingår i: Aquatic Toxicology. - : Elsevier BV. - 0166-445X. ; 159, s. 198-207
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Tidskriftsartikel (refereegranskat)abstract
- Killifish survive and reproduce in the New Bedford Harbor (NBH) in Massachusetts (MA), USA, a site severely contaminated with polychlorinated biphenyls (PCBs) for decades. Levels of 22 different PCB congeners were analyzed in liver from killifish collected in 2008. Concentrations of dioxin-like PCBs in liver of NBH killifish were ~400 times higher, and the levels of non-dioxin-like PCBs ~3000 times higher than in killifish from a reference site, Scorton Creek (SC), MA. The NBH killifish are known to be resistant to the toxicity of dioxin-like compounds and to have a reduced aryl hydrocarbon receptor (AhR) signaling response. Little is known about the responses of these fish to non-dioxin-like PCBs, which are at extraordinarily high levels in NBH fish. In mammals, some non-dioxin-like PCB congeners act through nuclear receptor 1I2, the pregnane-X-receptor (PXR). To explore this pathway in killifish, a PXR cDNA was sequenced and its molecular phylogenetic relationship to other vertebrate PXRs was determined. Killifish were also collected in 2009 from NBH and SC, and after four months in the laboratory they were injected with a single dose of either the dioxin-like PCB 126 (an AhR agonist) or the non-dioxin-like PCB 153 (a mammalian PXR agonist). Gills and liver were sampled three days after injection and transcript levels of PXR, cytochrome P450 3A (CYP3A), P-glycoprotein (Pgp), AhR2 and cytochrome P450 1A (CYP1A) were measured by quantitative PCR. As expected, there was little effect of PCB exposure on AhR2 or CYP1A in liver and gills of NBH fish. In NBH fish, but not in SC fish, there was increased expression of hepatic PXR, CYP3A and Pgp genes upon exposure to either of the two PCB congeners. However, basal PXR and Pgp mRNA levels in liver of NBH fish were significantly lower than in SC fish. A different pattern was seen in gills, where there were no differences in basal expression of these genes between the two populations. In SC fish, but not in NBH fish, there was increased expression of branchial PXR and CYP3A upon exposure to PCB126 and of CYP3A upon exposure to PCB153. The results suggest a difference between the two populations in non-AhR transcription factor signaling in liver and gills, and that this could involve killifish PXR. It also implies possible cross-regulatory interactions between that factor (presumably PXR) and AhR2 in liver of these fish.
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| 6. |
- Svensson, Ola, 1971-, et al.
(författare)
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Immigrant reproductive dysfunction facilitates ecological speciation
- 2017
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Ingår i: Evolution. - : Wiley-Blackwell. - 0014-3820 .- 1558-5646. ; 71:10, s. 2510-2521
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Tidskriftsartikel (refereegranskat)abstract
- The distributions of species are not only determined by where they can survive - they must also be able to reproduce. Although immigrant inviability is a well-established concept, the fact that immigrants also need to be able to effectively reproduce in foreign environments has not been fully appreciated in the study of adaptive divergence and speciation. Fertilization and reproduction are sensitive life history stages that could be detrimentally affected for immigrants in non-native habitats. We propose that 'immigrant reproductive dysfunction' is a hitherto overlooked aspect of reproductive isolation caused by natural selection on immigrants. This idea is supported by results from experiments on an externally fertilizing fish (sand goby, Pomatoschistus minutus). Growth and condition of adults were not affected by non-native salinity whereas males spawning as immigrants had lower sperm motility and hatching success than residents. We interpret these results as evidence for local adaptation or acclimation of sperm, and possibly also components of paternal care. The resulting loss in fitness, which we call 'immigrant reproductive dysfunction', has the potential to reduce gene flow between populations with locally adapted reproduction, and it may play a role in species distributions and speciation.
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| 7. |
- Wang, Xiaoyan, et al.
(författare)
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PAHs and PCBs residues and consumption risk assessment in farmed yellow croaker (Larimichthys crocea) from the East China Sea, China.
- 2019
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Ingår i: Marine pollution bulletin. - : Elsevier BV. - 1879-3363 .- 0025-326X. ; 140, s. 294-300
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Tidskriftsartikel (refereegranskat)abstract
- Large yellow croaker (Larimichthys crocea) purchased from five different farming sites in Zhoushan Archipelago and Xiangshan Harbor in the East China Sea, China were analyzed for polycyclic aromatic hydrocarbons (PAHs) and polychlorinated biphenyls (PCBs). Concentrations of PAHs and PCBs in the edible muscle of L. crocea ranged from 83.14 to 174.68ng/g wet weight (or 266.89 to 695.24ng/g dry weight) and 3.89 to 17.40ng/g wet weight (or 15.50 to 54.25ng/g dry weight), respectively. Incremental lifetime cancer risk (ILCR) associated with the dietary intake of PAHs and PCBs in L. crocea was assessed. Results showed that levels of PAHs in L. crocea were high enough to cause potential carcinogenic risks for human consumption, while, levels of PCBs in fish samples were of low significant carcinogenic risk.
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