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| 32. |
- Gunnarsson, Lina-Maria, 1977, et al.
(författare)
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Pharmaceutical industry effluent diluted 1:500 affects global gene expression, cytochrome P4501A activity and plasma phosphate in fish
- 2009
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Ingår i: Environmental Toxicology and Chemistry. - : Society of Environmental Toxicology and Chemistry (SETAC). - 0730-7268 .- 1552-8618. ; 28:12, s. 2639-2647
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Tidskriftsartikel (refereegranskat)abstract
- Patancheru, near Hyderabad, India, is a major production site for the global bulk drug market. Approximately 90 manufacturers send their wastewater to a common treatment plant in Patancheru. Extraordinary high levels of a wide range of pharmaceuticals have recently been demonstrated in the treated effluent. As little as 0.2% of this effluent can strongly reduce the growth rate of tadpoles, but the underlying mechanisms of toxicity are not known. To begin addressing how the effluent affects aquatic vertebrates, rainbow trout (Oncorhynchus mykiss) were exposed to 0.2% effluent for five days. Several physiological endpoints, together with effects on global hepatic gene expression patterns, were analyzed. The exposed fish showed both an induction of hepatic cytochrome P450 1A (CYP1A) gene expression, as well as enzyme activity. Clinical blood chemistry analyses revealed an increase in plasma phosphate levels, which in humans indicates impaired kidney function. Several oxidative stress-related genes were induced in the livers; however, no significant changes in antioxidant enzyme activities or in the hepatic glutathione levels were found. Furthermore, estrogen-regulated genes were slightly up-regulated following exposure, and moderate levels of estriol were detected in the effluent. The present study identifies changes in gene expression triggered by exposure to a high dilution of the effluent, supporting the hypothesis that these fish are responding to chemical exposure. The pattern of regulated genes may contribute to the identification of mechanisms of sub-lethal toxicity, as well as illuminate possible causative agents.
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| 33. |
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| 34. |
- Gunnarsson, Lina-Maria, 1977, et al.
(författare)
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Sensitive and robust gene expression changes in fish exposed to estrogen – a microarray approach
- 2007
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Ingår i: BMC Genomics. - : Springer Science and Business Media LLC. - 1471-2164. ; 8:149
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Tidskriftsartikel (refereegranskat)abstract
- Background Vitellogenin is a well established biomarker for estrogenic exposure in fish. However, effects on gonadal differentiation at concentrations of estrogen not sufficient to give rise to a measurable vitellogenin response suggest that more sensitive biomarkers would be useful. Induction of zona pellucida genes may be more sensitive but their specificities are not as clear. The objective of this study was to find additional sensitive and robust candidate biomarkers of estrogenic exposure. Results Hepatic mRNA expression profiles were characterized in juvenile rainbow trout exposed to a measured concentration of 0.87 and 10 ng ethinylestradiol/L using a salmonid cDNA microarray. The higher concentration was used to guide the subsequent identification of generally more subtle responses at the low concentration not sufficient to induce vitellogenin. A meta-analysis was performed with data from the present study and three similar microarray studies using different fish species and platforms. Within the generated list of presumably robust responses, several well-known estrogen-regulated genes were identified. Two genes, confirmed by quantitative RT-PCR (qPCR), fulfilled both the criteria of high sensitivity and robustness; the induction of the genes encoding zona pellucida protein 3 and a nucleoside diphosphate kinase (nm23). Conclusion The cross-species, cross-platform meta-analysis correctly identified several robust responses. This adds confidence to our approach used for identifying candidate biomarkers. Specifically, we propose that analyses of an nm23 gene together with zona pellucida genes may increase the possibilities to detect an exposure to low levels of estrogenic compounds in fish.
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| 35. |
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| 36. |
- Hanson, Niklas, 1976, et al.
(författare)
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Evaluation of long-term biomarker data from Perch (Perca fluviatilis) in the Baltic Sea suggests increasing exposure to environmental pollutants
- 2009
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Ingår i: Environmental Toxicology and Chemistry. - : Wiley. - 1552-8618 .- 0730-7268. ; 28:2, s. 364-373
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Tidskriftsartikel (refereegranskat)abstract
- Since 1988, biomarkers in female perch (Perca fluviatilis) have been analyzed at a reference site on the Swedish Baltic coast. Strong time trends toward increasing hepatic ethoxyresorufin-O-deethylase (EROD) activity and reduced gonadosomatic index (GSI) have been observed. This could be caused by pollutants as well as other factors, such as increasing water temperature or reduced mean age of sampled fish. Correlation analyses were used to find the most probable explanation for the time trends. The time trends were still significant for EROD (p < 0.001) and GSI (p < 0.001) when the correlations were controlled for age. Furthermore, increasing water temperature could not explain the time trends. Exposure to pollutants through runoff from land was found to be probable, because mean flow rate in a nearby river during the last 20 d before sampling correlated to EROD activity (p < 0.01). In addition, the sum of EROD activities during the life time of the perch (ERODlife) correlated significantly with GSI (p < 0.001). This suggests that perch exposed to more EROD-inducing chemicals during their lifetime have reduced or delayed gonad development. The time trend in GSI and the correlation between ERODlife and GSI were supported by data from a site in the Bothnian Bay (northern Baltic Sea; p < 0.05). The results indicate that increased rain fall (climate change) can affect the distribution and bioavailability of chemicals in coastal areas. The link between EROD and gonad size supports the common assumption that biochemical biomarkers can act as early warning signals for effects on higher levels, which commonly is difficult to show. The significant results can probably be attributed to the unique 20-year data set.
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| 37. |
- Hansson, T., et al.
(författare)
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Long-term monitoring of the health status of female perch (Perca fluviatilis) in the Baltic Sea shows decreased gonad weight and increased hepatic EROD activity
- 2006
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Ingår i: Aquatic Toxicology. - : Elsevier BV. - 0166-445X. ; 79:4, s. 341-355
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Tidskriftsartikel (refereegranskat)abstract
- Annual investigations of the health status of female perch (Perca fluviatilis) were performed during 8-13 years in order to detect long-term, large-scale changes in the Baltic Sea. These background data are also meant to be used as baselines in recipient investigations at various point sources in the Baltic Sea. Fish were sampled at three coastal sites in Sweden: two in the Baltic Proper (since 1988) and one in the Bothnian Bay (since 1993). In all, 19 biochemical, physiological and histopathological variables were measured. By reflecting central functions of life, such as red blood cell functions, immune defence, liver function, biotransformation processes, intermediary metabolism, ion balance, and reproduction, the selected variables give a good picture of the health status of the fish. The most important observations were strong trends towards decreased gonadosomatic index (relative gonad size) and increased hepatic EROD activity in female perch in the Baltic Proper. Most of the other variables varied little between the years. The reduced gonad size and the EROD induction indicate that factors in the environment, e.g. the occurrence of pollutants, affect important physiological functions, such as reproduction and biotransformation processes, in fish even in a reference area in the Baltic Proper. It is urgent to make further studies in order to identify which pollutant(s) or other possible cause(s) are responsible for the observed biological effects. (c) 2006 Elsevier B.V. All rights reserved.
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| 38. |
- Kling, Peter, 1968, et al.
(författare)
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Gender-specific proteomic responses in zebrafish liver following exposure to a selected mixture of brominated flame retardants
- 2008
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Ingår i: Ecotoxicology and Environmental Safety. - : Elsevier Inc. - 1090-2414 .- 0147-6513. ; 71:2, s. 319-27
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Tidskriftsartikel (refereegranskat)abstract
- Proteomic effect screening in zebrafish liver was performed to generate hypotheses following exposure (21 days) to a structurally diverse mixture of brominated flame retardants (BFRs). Fish were exposed to two doses (10 and 100 nmol/g feed). Two-dimensional gel-electrophoresis, image analysis and MALDI-TOF mass-spectrometry revealed 13 and 19 significant responses in males and females, respectively. Effects on proteins related to cellular maintenance and stress were observed in both genders. Regulated proteins were gender-specific, but functionally indicated common protective responses (peroxiredoxin 6 and Zgc:92891 in males and transketolase in females) suggesting oxidative stress. Betaine homocysteine methyltransferase (BHMT) was induced in both genders. In addition a female-specific downregulation of ironhomeostatic proteins (iron-regulatory protein 1 and transferrin) were observed. Our proteomic approach revealed novel responses that suggest important gender-specific sensitivity to BFRs that should be considered when interpreting adverse effects of BFRs.
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| 39. |
- Kling, Peter, 1968, et al.
(författare)
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Proteomic studies in zebrafish liver cells exposed to the brominated flame retardants HBCD and TBBPA.
- 2009
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Ingår i: Ecotoxicology and environmental safety. - : Elsevier BV. - 1090-2414 .- 0147-6513. ; 72:7, s. 1985-93
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Tidskriftsartikel (refereegranskat)abstract
- Proteomic effect screening in zebrafish liver cells was performed to generate hypotheses regarding single and mixed exposure to the BFRs HBCD and TBBPA. Responses at sublethal exposure were analysed by two-dimensional gel electrophoresis followed by MALDI-TOF and FT-ICR protein identification. Mixing of HBCD and TBBPA at sublethal doses of individual substances seemed to increase toxicity. Proteomic analyses revealed distinct exposure-specific and overlapping responses suggesting novel mechanisms with regard to HBCD and TBBPA exposure. While distinct HBCD responses were related to decreased protein metabolism, TBBPA revealed effects related to protein folding and NADPH production. Overlapping responses suggest increased gluconeogenesis (GAPDH and aldolase) while distinct mixture effects suggest a pronounced NADPH production and changes in proteins related to cell cycle control (prohibitin and crk-like oncogene). We conclude that mixtures containing HBCD and TBBPA may result in unexpected effects highlighting proteomics as a sensitive tool for detecting and hypothesis generation of mixture effects.
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| 40. |
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