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1.
Aquat Toxicol ; 265: 106741, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37944325

RESUMO

It is becoming increasingly recognised that contaminants are not isolated in their threats to the aquatic environment, with recent shifts towards studying the effects of chemical mixtures. In this study, adult marine mussels (Mytilus galloprovincialis) were exposed to two aqueous concentrations of the essential trace metal, Cu (5 and 32 µg L-1), and the non-essential metal, Pb (5 and 25 µg L-1), both individually and in binary mixtures. After a 14-day exposure, metal accumulation was determined in the digestive gland, gill and mantle tissues by inductively coupled plasma-mass spectrometry following acid digestion, and a number of biochemical, neurotoxic and physiological markers were assessed. These included measurements of DNA damage using comet assay, total glutathione concentration, acetylcholinesterase (AChE) activity and clearance rate. Metal accumulation was greater in the digestive gland and gill than in the mantle, and based on computed free ion concentrations, was greater for Pb than for Cu. Copper exhibited an inhibitory effect on Pb accumulation but Pb did not appear to affect Cu accumulation. Comet assay results revealed DNA damage (i.e., genotoxic effects) in all treatments but differences between the exposures were not significant (p > 0.05), and there were no significant differences in AChE activities between treatments. The most distinctive impacts were a reduction in clearance rate resulting from the higher concentration of Cu, with and without Pb, and an increase in glutathione in the gill resulting from the higher concentration of Cu without Pb. Multivariate analysis facilitated the development of a conceptual model based on the current findings and previously published data on the toxicity and intracellular behaviour of Cu and Pb that will assist in the advancement of regulations and guidelines regarding multiple metal contaminants in the environment.


Assuntos
Mytilus , Poluentes Químicos da Água , Animais , Cobre/toxicidade , Cobre/análise , Chumbo/toxicidade , Acetilcolinesterase , Poluentes Químicos da Água/toxicidade , Dano ao DNA , Glutationa
2.
Chemosphere ; 303(Pt 2): 134914, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35588874

RESUMO

During the decommissioning and removal of radioactive material in nuclear facilities, fine, tritiated dusts of stainless steel, cement or tungsten are generated that could be accidently released to the environment. However, the potential radio- and ecotoxicological effects these tritiated particles may have are unknown. In this study, stainless steel particles (SSPs) representative of those likely to be tritiated are manufactured by hydrogenation and their tissue-specific bioaccumulation, release (depuration) and subsequent genotoxic response have been studied in the marine mussel, Mytilus galloprovincialis, as a baseline for future assessments of the potential effects of tritiated SSPs. Exposure to 1000 µg L-1 of SSPs and adopting Cr as a proxy for stainless steel revealed relatively rapid accumulation (∼5 h) in the various mussel tissues but mostly in the digestive gland. Over longer periods up to 18 days, SSPs were readily rejected and egested as faecal material. DNA strand breaks, as a measure of genotoxicity, were determined at each time point in mussel haemocytes using single cell gel electrophoresis, or the comet assay. Lack of chemical genotoxicity was attributed to the rapid processing of SSP particles and limited dissolution of elemental components of steel. Further work employing tritiated SSPs will enable radio-toxicology to be studied without the confounding effects of chemical toxicity.


Assuntos
Mytilus , Aço Inoxidável , Animais , Bioacumulação , Ensaio Cometa/métodos , Dano ao DNA
3.
Int J Radiat Biol ; 98(6): 1185-1200, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-32659186

RESUMO

The objective of this paper is to present the results of discussions at a workshop held as part of the International Congress of Radiation Research (Environmental Health stream) in Manchester UK, 2019. The main objective of the workshop was to provide a platform for radioecologists to engage with radiobiologists to address major questions around developing an Ecosystem approach in radioecology and radiation protection of the environment. The aim was to establish a critical framework to guide research that would permit integration of a pan-ecosystem approach into radiation protection guidelines and regulation for the environment. The conclusions were that the interaction between radioecologists and radiobiologists is useful in particular in addressing field versus laboratory issues where there are issues and challenges in designing good field experiments and a need to cross validate field data against laboratory data and vice versa. Other main conclusions were that there is a need to appreciate wider issues in ecology to design good approaches for an ecosystems approach in radioecology and that with the capture of 'Big Data', novel tools such as machine learning can now be applied to help with the complex issues involved in developing an ecosystem approach.


Assuntos
Proteção Radiológica , Ecologia , Ecossistema
4.
Int J Radiat Biol ; 95(2): 120-143, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30614743

RESUMO

PURPOSE: Low level laser therapy (LLLT) in the visible to near infrared spectral band (390-1100 nm) is absorption of laser light at the electronic level, without generation of heat. It may be applied in a wide range of treatments including wound healing, inflammation and pain reduction. Despite its potential beneficial impacts, the use of lasers for therapeutic purposes still remains controversial in mainstream medicine. Whilst taking into account the physical characteristics of different qualities of lasers, this review aims to provide a comprehensive account of the current literature available in the field pertaining to their potential impact at cellular and molecular levels elucidating mechanistic interactions in different mammalian models. The review also aims to focus on the integral approach of the optimal characteristics of LLLT that suit a biological system target to produce the beneficial effect at the cellular and molecular levels. METHODS: Recent research articles were reviewed that explored the interaction of lasers (coherent sources) and LEDs (incoherent sources) at the molecular and cellular levels. RESULTS: It is envisaged that underlying mechanisms of beneficial impact of lasers to patients involves biological processes at the cellular and molecular levels. The biological impact or effects of LLLT at the cellular and molecular level could include cellular viability, proliferation rate, as well as DNA integrity and the repair of damaged DNA. This review summarizes the available information in the literature pertaining to cellular and molecular effects of lasers. CONCLUSIONS: It is suggested that a change in approach is required to understand how to exploit the potential therapeutic modality of lasers whilst minimizing its possible detrimental effects.


Assuntos
Terapia com Luz de Baixa Intensidade , Dano ao DNA , Reparo do DNA , Humanos , Lasers Semicondutores
5.
J Environ Radioact ; 192: 312-320, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30015316

RESUMO

With respect to environmental protection, understanding radionuclide bioconcentration is necessary to relate exposure to radiation dose and hence to biological responses. Few studies are available on tissue specific accumulation of short-lived radionuclides in aquatic invertebrates. Short-lived radionuclides such as 32Phosphorus (32P), although occurring in small quantities in the environment, are capable of concentrating in the biota, especially if they are chronically exposed. In this study, we firstly compared tissue specific bioaccumulation and release (depuration) of 32P in adult marine (Mytilus galloprovincialis, MG) and freshwater bivalve molluscs (Dreissena polymorpha, DP). Secondly, using the Environmental Risk from Ionising Contaminants Assessment and Management (ERICA) tool, we calculated tissue specific doses following determination of radionuclide concentration. Marine and freshwater bivalves were exposed for 10 days to varying 32P concentrations to acquire desired whole body average dose rates of 0.10, 1.0 and 10 mGy d-1. Dose rates encompass a screening dose rate value of 10 µGy h-1 (0.24 mGy d-1), in accordance with the ERICA tool. This study is the first to relate tissue specific uptake and release (via excretion) of 32P from two anatomically similar bivalve species. Results showed highly tissue specific accumulation of this radionuclide and similarity of accumulation pattern between the two species. Our data, which highlights preferential 32P accumulation in specific tissues such as digestive gland, demonstrates that in some cases, tissue-specific dose rates may be required to fully evaluate the potential effects of radiation exposure on non-human biota. Differential sensitivity between biological tissues could result in detrimental biological responses at levels presumed to be acceptable when adopting a 'whole-body' approach.


Assuntos
Bivalves/fisiologia , Radioisótopos de Fósforo/metabolismo , Poluentes Radioativos da Água/metabolismo , Animais , Água Doce , Doses de Radiação , Água do Mar
6.
Mutagenesis ; 32(1): 77-90, 2017 01.
Artigo em Inglês | MEDLINE | ID: mdl-28011749

RESUMO

We used the marine bivalve (Mytilus galloprovincialis) to assess a range of biological or biomarker responses following exposure to a model-engineered nanoparticle, C60 fullerene, either alone or in combination with a model polycyclic aromatic hydrocarbon, benzo(α)pyrene [B(α)P]. An integrated biomarker approach was used that included: (i) determination of 'clearance rates' (a physiological indicator at individual level), (ii) histopathological alterations (at tissue level), (iii) DNA strand breaks using the comet assay (at cellular level) and (iv) transcriptional alterations of p53 (anti-oncogene) and ras (oncogene) determined by real-time quantitative polymerase chain reaction (at the molecular/genetic level). In addition, total glutathione in the digestive gland was measured as a proxy for oxidative stress. Here, we report that mussels showed no significant changes in 'clearance rates' after 1 day exposure, however significant increases in 'clearance rates' were found following exposure for 3 days. Histopathology on selected organs (i.e. gills, digestive glands, adductor muscles and mantles) showed increased occurrence of abnormalities in all tissues types, although not all the exposed organisms showed these abnormalities. Significantly, increased levels of DNA strand breaks were found after exposure for 3-days in most individuals tested. In addition, a significant induction for p53 and ras expression was observed in a tissue and chemical-specific pattern, although large amounts of inter-individual variability, compared with other biomarkers, were clearly apparent. Overall, biological responses at different levels showed variable sensitivity, with DNA strand breaks and gene expression alterations exhibiting higher sensitivities. Furthermore, the observed genotoxic responses were reversible after a recovery period, suggesting the ability of mussels to cope with the toxicants C60 and/or B(α)P under our experimental conditions. Overall, in this comprehensive study, we have demonstrated mussels as a suitable model marine invertebrate species to study the potential detrimental effects induced by possible genotoxicants and toxicants, either alone or in combinations at different levels of biological organisation (i.e. molecular to individual levels).


Assuntos
Bivalves/efeitos dos fármacos , Dano ao DNA , Fulerenos/toxicidade , Proteína Supressora de Tumor p53/efeitos dos fármacos , Proteínas ras/efeitos dos fármacos , Animais , Benzo(a)pireno/farmacologia , Benzo(a)pireno/toxicidade , Bivalves/genética , Bivalves/metabolismo , Ensaio Cometa , DNA/efeitos dos fármacos , Fulerenos/farmacologia , Regulação da Expressão Gênica , Glutationa/análise , Glutationa/efeitos dos fármacos , Modelos Animais , Especificidade de Órgãos , Estresse Oxidativo/efeitos dos fármacos , Proteína Supressora de Tumor p53/genética , Proteínas ras/genética
7.
Artigo em Inglês | MEDLINE | ID: mdl-27692298

RESUMO

Auranofin, an organogold compound classified as an anti-rheumatic agent is under phase 2 clinical trials for re-purposing to treat recurrent epithelial ovarian cancer. We have reported earlier that Breast cancer 1, early onset (BRCA1) mutant ovarian cancer cells exhibit increased sensitivity to auranofin. BRCA1 is a DNA repair protein whose functional status is critical in the prognosis of ovarian cancer. Apart from DNA repair capability of cancer cells, membrane fluidity is also implicated in modulating resistance to chemotherapeutics. We report here that membrane fluidity influences the sensitivity of ovarian cancer cell lines, OVCAR5 and IGROV1, to auranofin. Electron spin resonance (ESR) analysis revealed a more fluidized membrane in IGROV1 compared to OVCAR5. Interestingly, IGROV1 cells were more sensitive to auranofin induced cytotoxicity than OVCAR5. In comparison to OVCAR5, IGROV1 cells also exhibited an increased number of DNA double strand breaks (DSBs) upon auranofin treatment as assessed by 53BP1 immunostaining. Furthermore, correlation analysis demonstrated a strong positive correlation (r=0.856) between membrane fluidity and auranofin sensitivity in these cell lines. Auranofin-treated IGROV1 cells also exhibited increased cellular oxidation and apoptosis. Anti-oxidant, N-acetyl cysteine (NAC) inhibited the cellular oxidation and apoptosis in auranofin-treated ovarian cancer cells suggesting reactive oxygen species (ROS) mediate the anti-cancer properties of auranofin. Overall, our study suggests that auranofin mediates its cytotoxicity via ROS production in ovarian cancer cells which correlates positively with membrane fluidity.


Assuntos
Antirreumáticos/farmacologia , Apoptose/efeitos dos fármacos , Auranofina/farmacologia , Dano ao DNA/efeitos dos fármacos , Fluidez de Membrana/efeitos dos fármacos , Testes de Mutagenicidade/métodos , Neoplasias Ovarianas/patologia , Feminino , Humanos , Neoplasias Ovarianas/tratamento farmacológico , Espécies Reativas de Oxigênio/metabolismo , Células Tumorais Cultivadas
8.
Environ Sci Technol ; 50(5): 2700-8, 2016 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-26829245

RESUMO

Dechlorane Plus (DP) is a proposed alternative to the legacy flame retardant decabromodiphenyl ether (BDE-209), a major component of Deca-BDE formulations. In contrast to BDE-209, toxicity data for DP are scarce and often focused on mice. Validated dietary in vivo exposure of the marine bivalve (Mytilus galloprovincialis) to both flame retardants did not induce effects at the physiological level (algal clearance rate), but induced DNA damage, as determined by the comet assay, at all concentrations tested. Micronuclei formation was induced by both DP and BDE-209 at the highest exposure concentrations (100 and 200 µg/L, respectively, at 18% above controls). DP caused effects similar to those by BDE-209 but at lower exposure concentrations (5.6, 56, and 100 µg/L for DP and 56, 100, and 200 µg/L for BDE-209). Moreover, bioaccumulation of DP was shown to be concentration dependent, in contrast to BDE-209. The results described suggest that DP poses a greater genotoxic potential than BDE-209.


Assuntos
Éteres Difenil Halogenados/toxicidade , Hidrocarbonetos Clorados/toxicidade , Mytilus/efeitos dos fármacos , Compostos Policíclicos/toxicidade , Animais , Ensaio Cometa , Dano ao DNA/efeitos dos fármacos , Ecotoxicologia/métodos , Exposição Ambiental/efeitos adversos , Retardadores de Chama/farmacocinética , Retardadores de Chama/toxicidade , Éteres Difenil Halogenados/farmacocinética , Hidrocarbonetos Clorados/farmacocinética , Testes de Mutagenicidade/métodos , Mytilus/fisiologia , Compostos Policíclicos/farmacocinética
9.
PLoS One ; 11(2): e0149492, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26900704

RESUMO

Advanced in vitro culture from tissues of different origin includes three-dimensional (3D) organoid micro structures that may mimic conditions in vivo. One example of simple 3D culture is spheroids; ball shaped structures typically used as liver and tumour models. Oxygen is critically important in physiological processes, but is difficult to quantify in 3D culture: and the question arises, how small does a spheroid have to be to have minimal micro-environment formation? This question is of particular importance in the growing field of 3D based models for toxicological assessment. Here, we describe a simple non-invasive approach modified for the quantitative measurement and subsequent evaluation of oxygen gradients in spheroids developed from a non-malignant fish cell line (i.e. RTG-2 cells) using Electron Paramagnetic Resonance (EPR) oximetry. Sonication of the paramagnetic probe Lithium phthalocyanine (LiPc) allows for incorporation of probe particulates into spheroid during its formation. Spectra signal strength after incorporation of probe into spheroid indicated that a volume of 20 µl of probe (stock solution: 0.10 mg/mL) is sufficient to provide a strong spectra across a range of spheroid sizes. The addition of non-toxic probes (that do not produce or consume oxygen) report on oxygen diffusion throughout the spheroid as a function of size. We provide evidence supporting the use of this model over a range of initial cell seeding densities and spheroid sizes with the production of oxygen distribution as a function of these parameters. In our spheroid model, lower cell seeding densities (∼2,500 cells/spheroid) and absolute size (118±32 µm) allow control of factors such as pre-existing stresses (e.g. ∼ 2% normoxic/hypoxic interface) for more accurate measurement of treatment response. The applied methodology provides an elegant, widely applicable approach to directly characterize spheroid (and other organoid) cultures in biomedical and toxicological research.


Assuntos
Espectroscopia de Ressonância de Spin Eletrônica/métodos , Oximetria/métodos , Oxigênio/metabolismo , Esferoides Celulares/citologia , Esferoides Celulares/metabolismo , Animais , Linhagem Celular , Oncorhynchus mykiss
10.
J Environ Radioact ; 155-156: 1-6, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-26874225

RESUMO

Accurate dosimetry is critically important for ecotoxicological and radioecological studies on the potential effects of environmentally relevant radionuclides, such as tritium ((3)H). Previous studies have used basic dosimetric equations to estimate dose from (3)H exposure in ecologically important organisms, such as marine mussels. This study compares four different methods of estimating dose to adult mussels exposed to 1 or 15 MBq L(-1) tritiated water (HTO) under laboratory conditions. These methods were (1) an equation converting seawater activity concentrations to dose rate with fixed parameters; (2) input into the ERICA tool of seawater activity concentrations only; (3) input into the ERICA tool of estimated whole organism concentrations (woTACs), comprising dry activity plus estimated tissue free water tritium (TFWT) activity (TFWT volume × seawater activity concentration); and (4) input into the ERICA tool of measured whole organism activity concentrations, comprising dry activity plus measured TFWT activity (TFWT volume × TFWT activity concentration). Methods 3 and 4 are recommended for future ecotoxicological experiments as they produce values for individual animals and are not reliant on transfer predictions (estimation of concentration ratio). Method 1 may be suitable if measured whole organism concentrations are not available, as it produced results between 3 and 4. As there are technical complications to accurately measuring TFWT, we recommend that future radiotoxicological studies on mussels or other aquatic invertebrates measure whole organism activity in non-dried tissues (i.e. incorporating TFWT and dry activity as one, rather than as separate fractions) and input this data into the ERICA tool.


Assuntos
Ecotoxicologia/métodos , Mytilus/efeitos da radiação , Doses de Radiação , Trítio/análise , Animais , Água do Mar , Poluentes Radioativos da Água/análise
11.
Mutat Res ; 784-785: 8-15, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26731315

RESUMO

Auranofin, a thioredoxin reductase inhibitor and an anti-rheumatic drug is currently undergoing phase 2 clinical studies for repurposing to treat recurrent epithelial ovarian cancer. Previous studies have established that auranofin exerts its cytotoxic activity by increasing the production of reactive oxygen species (ROS). Breast cancer 1, early onset (BRCA1) is a DNA repair protein whose functional status is critical in the prognosis of ovarian cancer. Apart from its key role in DNA repair, BRCA1 is also known to modulate cellular redox homeostasis by regulating the stability of anti-oxidant transcription factor, nuclear factor erythroid 2-related factor 2 (Nrf2) via direct protein-protein interaction. However, it is currently unknown whether BRCA1 modulates the sensitivity of ovarian cancer cells to auranofin. Here we report that BRCA1-depleted cells exhibited increased DNA double strand breaks (DSBs) and decreased clonogenic cell survival upon auranofin treatment. Interestingly, auranofin induced the expression of Nrf2 in BRCA1-depleted cells suggesting its regulation independent of BRCA1. Furthermore, anti-oxidant agent, N-acetyl cysteine (NAC) protected BRCA1-depleted cells from DNA damage and apoptosis induced by auranofin. Our study suggests that accumulated lethal DSBs resulting from the oxidative damage render BRCA1 deficient cells more sensitive to auranofin despite the activation of Nrf2.


Assuntos
Auranofina/farmacologia , Proteína BRCA1/genética , Neoplasias Ovarianas/tratamento farmacológico , Acetilcisteína/farmacologia , Antioxidantes/farmacologia , Apoptose/efeitos dos fármacos , Apoptose/genética , Proteína BRCA1/metabolismo , Carcinoma Epitelial do Ovário , Linhagem Celular Tumoral/efeitos dos fármacos , Quebras de DNA de Cadeia Dupla/efeitos dos fármacos , Dano ao DNA/efeitos dos fármacos , Dano ao DNA/genética , Feminino , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Fator 2 Relacionado a NF-E2/genética , Fator 2 Relacionado a NF-E2/metabolismo , Neoplasias Epiteliais e Glandulares/tratamento farmacológico , Neoplasias Epiteliais e Glandulares/genética , Neoplasias Epiteliais e Glandulares/patologia , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/patologia
12.
Mar Pollut Bull ; 95(2): 688-98, 2015 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-25843441

RESUMO

Marine organisms are exposed to low doses of anthropogenic contaminants during their entire life. Authorized amounts of radionuclides are discharged in the Channel by nuclear facilities. The Pacific oyster was used to investigate the potential impact of chronic exposure to ionizing radiation. Though we exposed larvae and spat for two weeks to much higher concentrations than those encountered near nuclear facilities, oyster growth and expression of 9 selected stress genes were not significantly changed. To determine potential DNA damage, 2year old oysters were exposed for two weeks to tritiated water. The comet assay was used to evaluate the level of DNA strand breaks in haemocytes, whilst the 'clearance rate' was used as a measure of physiological effects. Whilst other parameters did not alter, DNA damage significantly increased. Our results highlight the significance of the observed DNA damage and their potential consequences at higher levels of biological organization.


Assuntos
Crassostrea/fisiologia , Radiação Ionizante , Estresse Fisiológico/genética , Poluentes Radioativos da Água/toxicidade , Animais , Ensaio Cometa , Crassostrea/metabolismo , Dano ao DNA , Expressão Gênica , Mutagênicos/toxicidade , Monitoramento de Radiação , Testes de Toxicidade Crônica
13.
Chemosphere ; 112: 256-66, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-25048914

RESUMO

Uptake and discharge of ballast water by ocean-going ships contribute to the worldwide spread of aquatic invasive species, with negative impacts on the environment, economies, and public health. The International Ballast Water Management Convention aims at a global answer. The agreed standards for ballast water discharge will require ballast water treatment. Systems based on various physical and/or chemical methods were developed for on-board installation and approved by the International Maritime Organization. Most common are combinations of high-performance filters with oxidizing chemicals or UV radiation. A well-known problem of oxidative water treatment is the formation of disinfection by-products, many of which show genotoxicity, carcinogenicity, or other long-term toxicity. In natural biota, genetic damages can affect reproductive success and ultimately impact biodiversity. The future exposure towards chemicals from ballast water treatment can only be estimated, based on land-based testing of treatment systems, mathematical models, and exposure scenarios. Systematic studies on the chemistry of oxidants in seawater are lacking, as are data about the background levels of disinfection by-products in the oceans and strategies for monitoring future developments. The international approval procedure of ballast water treatment systems compares the estimated exposure levels of individual substances with their experimental toxicity. While well established in many substance regulations, this approach is also criticised for its simplification, which may disregard critical aspects such as multiple exposures and long-term sub-lethal effects. Moreover, a truly holistic sustainability assessment would need to take into account factors beyond chemical hazards, e.g. energy consumption, air pollution or waste generation.


Assuntos
Navios , Eliminação de Resíduos Líquidos/métodos , Poluentes Químicos da Água , Animais , Desinfecção , Exposição Ambiental/efeitos adversos , Exposição Ambiental/análise , Humanos , Medição de Risco , Poluentes Químicos da Água/análise , Poluentes Químicos da Água/toxicidade
14.
Mutat Res ; 754(1-2): 22-31, 2013 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-23591161

RESUMO

Nickel (Ni) is a known carcinogenic and mutagenic compound and an important contaminant of aquatic environments. Ni toxicity and its potential impact on aquatic organisms are, however, not well understood. This study used an integrated approach to evaluate genotoxic effects, tissue-specific accumulation and transcriptional profiles of key genes in mussels, Mytilus galloprovincialis, exposed to a range of concentrations of Ni. The genotoxic effects assessed were total and oxidative DNA damage (DNA strand breaks measured using the enzyme modified comet assay), and induction of micronuclei (MN; clastogenic and/or aneugenic effects) using haemocytes as the target cells. Six genes (pgp, mt10, mt20, sod, hsp70 and gst) were selected for transcriptional analysis in the gills based on their key role in the stress response. Following exposure to sublethal concentrations of Ni (0-3600µgL(-1)) for 5 days, mussel haemocytes showed significant genotoxicity at >1800µgL(-1) (4-fold increase for DNA strand breaks and 3-fold increase for MN induction). There was no significant difference between buffer (control) and enzyme treatments which target oxidised DNA bases (formamidopyrimidine glycosylase or endonuclease IIII). This suggested that, in haemocytes, oxidative DNA damage is not a major mechanism for Ni-induced genotoxicity. The expression of mt20 and gst genes in gill was up-regulated at genotoxic concentrations, whilst pgp expression was markedly up-regulated, particularly at 18µgL(-1) Ni (19-fold increase). Pearson's correlation analysis revealed significant associations between % tail DNA and MN induction in haemocytes (r=0.88, p<0.05), and between Ni accumulation in foot (r=0.47, p<0.05) and digestive gland (r=0.41, p<0.05) and induction of MN in the haemocytes. Our results are the first to suggest that Ni-induced genotoxicity in mussel haemocytes may not be a result of oxidative DNA damage, and that multixenobiotic resistance (MXR) may play an important role in Ni detoxification in this species.


Assuntos
Biomarcadores/metabolismo , Bivalves/efeitos dos fármacos , Dano ao DNA , Níquel/toxicidade , Estresse Oxidativo , Transcrição Gênica/efeitos dos fármacos , Animais , Sequência de Bases , Bivalves/genética , Ensaio Cometa , Primers do DNA , Espectrometria de Massas , Reação em Cadeia da Polimerase em Tempo Real
15.
Environ Pollut ; 168: 107-12, 2012 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-22609861

RESUMO

There is growing concern over the potential detrimental impact of ionizing radiation on natural biota. The mechanistic cause-and-effect impact of ionizing radiation has yet to be characterized in any aquatic species. Adopting an integrated approach, including radiochemical analysis of environmental samples, we evaluate molecular responses to ionizing radiation in the marine mussel, Mytilus edulis. These responses included analyses of RAD51 mRNA expression, a gene involved in the repair of DNA double strand breaks, and induction of DNA strand breaks using the comet assay, in samples collected from a site impacted by low level ionizing radiation discharges. Based on activities of the radionuclides measured in sediment and mussel tissue at the discharge site, external and internal dose rates were low, at ca. 0.61 µGyh(-1) and significantly lower than the generic (all species) "no effect" dose rate of 10 uGyh(-1), yet DNA strand breakage and RAD51 mRNA expression were both altered.


Assuntos
Mytilus edulis/efeitos da radiação , Radiação Ionizante , Poluentes Radioativos da Água/toxicidade , Animais , Ensaio Cometa , Dano ao DNA , Relação Dose-Resposta à Radiação , Sedimentos Geológicos/química , Mytilus edulis/genética , Mytilus edulis/metabolismo , RNA Mensageiro/metabolismo , Rad51 Recombinase/genética , Rad51 Recombinase/metabolismo , Poluentes Radioativos da Água/análise , Poluentes Radioativos da Água/metabolismo
16.
Radiat Res ; 177(5): 693-716, 2012 May.
Artigo em Inglês | MEDLINE | ID: mdl-22214380

RESUMO

There is growing scientific, regulatory and public concern over anthropogenic input of radionuclides to the aquatic environment, especially given the issues surrounding existing nuclear waste, future energy demand and past or potential nuclear accidents. A change in the approach to how we protect the environment from ionizing radiation has also underlined the importance of assessing its impact on nonhuman biota. This review presents a thorough and critical examination of the available information on the effects of ionizing radiation on aquatic invertebrates, which constitute approximately 90% of extant life on the planet and play vital roles in ecosystem functioning. The aim of the review was to assess the progress made so far, addressing any concerns and identifying the knowledge gaps in the field. The critical analysis of the available information included determining yearly publications in the field, qualities of radiation used, group(s) of animals studied, and levels of biological organization at which effects were examined. The overwhelming conclusion from analysis of the available information is that more data are needed in almost every area. However, in light of the current priorities in human and environmental health, and considering regulatory developments, the following are areas of particular interest for future research on the effects of ionizing radiation on nonhuman biota in general and aquatic invertebrates in particular: (1) studies that use end points across multiple levels of biological organization, including an ecosystem level approach where appropriate, (2) multiple species studies that produce comparable data across phylogenetic groups, and (3) determination of the modifying (i.e. antagonistic, additive or synergistic) effects of biotic and abiotic factors on the impact of ionizing radiation. It is essential that all of these issues are examined in the context of well-defined radiation exposure and total doses received and consider the life stages and life span of the species studied. The review also provides future directions for studies in this stimulating area of research to protect human and environmental health.


Assuntos
Organismos Aquáticos/efeitos da radiação , Invertebrados/efeitos da radiação , Radiação Ionizante , Animais , Apoptose/efeitos da radiação , Comportamento Animal/efeitos da radiação , Biota , Relação Dose-Resposta à Radiação , Previsões , Invertebrados/fisiologia , Dose Letal Mediana , Muda/efeitos da radiação , Mutagênese , Tolerância a Radiação , Eficiência Biológica Relativa , Reprodução/efeitos da radiação , Salinidade , Especificidade da Espécie , Temperatura , Poluentes Radioativos da Água/efeitos adversos
17.
Environ Pollut ; 162: 406-12, 2012 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-22243892

RESUMO

The tissue-specific accumulation and time-dependent depuration of radioactive (63)Ni by the byssus, gut, foot, gills, kidney, adductor muscle and faeces of Mytilus edulis has been investigated using a pulse-chase technique. The rate and extent of depuration of (63)Ni varied between tissues and, after 168 h, the concentration factors and assimilation efficiencies ranged from 1 to 35 L kg(-1) and 5%-13%, respectively. Mussels were also exposed to a range of environmentally-realistic concentrations of dissolved Ni, prior to the analysis of biological endpoints. The clearance rate was concentration-dependent and at the highest concentration decreased by 30%. Neutral red retention (NRR) assays indicated a cytotoxic response and DNA strand breaks were observed in the haemocytes. The association of DNA damage with that of physiological and cytotoxic effects suggests that Ni exerts a significant impact on Mytilus edulis at cellular and genetic levels.


Assuntos
Mytilus edulis/metabolismo , Níquel/metabolismo , Níquel/toxicidade , Poluentes Químicos da Água/metabolismo , Poluentes Químicos da Água/toxicidade , Animais , Dano ao DNA/efeitos dos fármacos , Hemócitos/efeitos dos fármacos , Hemócitos/metabolismo , Mytilus edulis/química , Mytilus edulis/efeitos dos fármacos , Mytilus edulis/genética , Níquel/análise , Especificidade de Órgãos , Água do Mar/análise , Poluentes da Água , Poluentes Químicos da Água/análise
18.
Mutat Res ; 745(1-2): 92-103, 2012 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-22230430

RESUMO

Whilst there is growing concern over the potential detrimental impact of engineered nanoparticles (ENPs) on the natural environment, little is known about their interactions with other contaminants. In the present study, marine mussels (Mytilus sp.) were exposed for 3 days to C(60) fullerenes (C(60); 0.10-1 mg l(-1)) and a model polycyclic aromatic hydrocarbon (PAH), fluoranthene (32-100 µg l(-1)), either alone or in combination. The first two experiments were conducted by exposing the organisms to different concentrations of C(60) and fluoranthene alone, in order to determine the effects on total glutathione levels (as a measure of generic oxidative stress), genotoxicity (DNA strand breaks using Comet assay in haemocytes), DNA adduct analyses (using (32)P-postlabelling method) in different organs, histopathological changes in different tissues (i.e. adductor muscle, digestive gland and gills) and physiological effects (feeding or clearance rate). Subsequently, in the third experiment, a combined exposure of C(60) plus fluoranthene (0.10 mg l(-1) and 32 µg l(-1), respectively) was carried out to evaluate all endpoints mentioned above. Both fluoranthene and C(60) on their own caused concentration-dependent increases in DNA strand breaks as determined by the Comet assay. Formation of DNA adducts however could not be detected for any exposure conditions. Combined exposure to C(60) and fluoranthene additively enhanced the levels of DNA strand breaks along with a 2-fold increase in the total glutathione content. In addition, significant accumulation of C(60) was observed in all organs, with highest levels in digestive gland (24.90 ± 4.91µg C(60) g(-1) ww). Interestingly, clear signs of abnormalities in adductor muscle, digestive gland and gills were observed by histopathology. Clearance rates indicated significant differences compared to the control with exposure to C(60), and C(60)/fluoranthene combined treatments, but not after fluoranthene exposure alone. This study demonstrated that at the selected concentrations, both C(60) and fluoranthene evoke toxic responses and genetic damage. The combined exposure produced enhanced damage with additive rather than synergistic effects.


Assuntos
Adutos de DNA/análise , Dano ao DNA/genética , Fluorenos/toxicidade , Fulerenos/toxicidade , Nanopartículas/toxicidade , Estresse Oxidativo/genética , Animais , Ensaio Cometa , Sistema Digestório/efeitos dos fármacos , Interações Medicamentosas , Fluorenos/administração & dosagem , Fulerenos/administração & dosagem , Brânquias/efeitos dos fármacos , Glutationa/metabolismo , Músculos/efeitos dos fármacos , Mytilus , Nanopartículas/administração & dosagem
19.
Environ Sci Technol ; 45(20): 8974-81, 2011 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-21899289

RESUMO

Marine mussels can develop hemeic and gonadal neoplasia in the natural environment. Associated with these diseases are the tumor suppressor (TS) p53 and the proto-oncogene ras coded proteins, both of which are highly conserved among molluscs and vertebrates. We report, for the first time, tissue-specific expression analysis of p53 and ras genes in Mytilus edulis by means of quantitative RT-PCR. A tissue-specific response was observed after 6 and 12 days exposure to a sublethal concentration of a model Polycyclic Aromatic Hydrocarbon (PAH), benzo(α)pyrene (B(α)P). This sublethal concentration (56 µg/L) was selected based on an integrated biomarker analysis carried out prior to gene expression analysis, which included a 'clearance rate' assay, histopathological analysis, and DNA strand break measurements. The results indicated that the selected concentration of B(α)P can lead to the induction of DNA strand breaks, tissue damage, and expression of tumor-regulating genes. Both p53 and ras are expressed in a tissue-specific manner, which collaborate with tissue-specific function in response to genotoxic stress. The integrated biological responses in Mytilus edulis strengthen the use of this organism to investigate the fundamental mechanism of development of malignancy in invertebrate which could be translated to other organisms including humans.


Assuntos
Benzo(a)pireno/toxicidade , Bivalves/efeitos dos fármacos , Bivalves/metabolismo , Proteína Supressora de Tumor p53/genética , Proteínas ras/genética , Animais , Monitoramento Ambiental , Proto-Oncogene Mas , Reação em Cadeia da Polimerase em Tempo Real
20.
Ecotoxicol Environ Saf ; 74(7): 1913-20, 2011 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-21851981

RESUMO

While copper (Cu) is considered to be an essential trace element for many organisms, overexposure to this metal can induce a wide spectrum of effects including DNA damage. Given that Cu is a highly relevant contaminant in the marine environment, we aimed to evaluate the induction of DNA strand breaks (using the comet assay) in haemocytes and concurrently also determined biological responses at higher levels of biological organisation in bivalve molluscs, Mytilus edulis, following exposure for 5 days to a range of environmentally realistic levels of Cu (18-56 µg l(-1)). Prior to evaluation of genetic damage, the maximum tolerated concentration (MTC) was also determined, which was found to be (100 µg l(-1)) above which complete mortality over the exposure period was observed. In addition to DNA damage, levels of glutathione in adductor muscle extracts, histopathological examination of various organs (viz., adductor muscle, gills and digestive glands) and clearance rates as a physiological measure at individual level were also determined. Furthermore, tissue-specific accumulation and levels of Cu in water samples were also determined using ICP-MS. There was a strong concentration-dependant induction for DNA damage and total glutathione levels increased by 1.8-fold at 56 µg l(-1) Cu. Histological examination of the organs showed qualitatively distinct abnormalities. Clearance rate also showed a significant decrease compared to controls even at the lowest concentration (i.e. 18 µg l(-1); P=0.003). Cu levels in adductor muscle (P=0.012), digestive gland (P=0.008) and gills (P=0.002) were significantly higher than in the control. The multi-biomarker approach used here suggests that in some cases clear relationships exist between genotoxic and higher level effects, which could be adopted as an integrated tool to evaluate different short and long-term toxic effects of pollutants.


Assuntos
Cobre/toxicidade , Dano ao DNA , Mytilus edulis/efeitos dos fármacos , Animais , Biomarcadores/análise , Ensaio Cometa , Cobre/farmacocinética , Exposição Ambiental/efeitos adversos , Brânquias/química , Brânquias/efeitos dos fármacos , Glutationa/análise , Hemócitos/efeitos dos fármacos , Músculos/química , Músculos/efeitos dos fármacos , Água do Mar/química , Distribuição Tecidual
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