Publicação
Molecular effects of metals and ionizing radiation on cells exposed in vitro to an effluent from a uranium mine
| Resumo: | We are constantly exposed to ionizing radiation in different ways, through both natural or artificial sources, which one possible source is the uranium mining activity. However, the disposal of uranium mining tailings has resulted in their accumulation in the environment and the accidental exposure of human and nonhuman biota to several metals and radionuclides. Several impacts may result from this type of exposure, which can ultimately cause DNA damage and possibly mutations that can lead to carcinogenesis. Additionally, the interaction between metals and radionuclides may result in synergistic effects, and the response mechanisms underlying still need to be understood. Therefore, the exposure to complex environmental matrices containing a mixture of metals and radionuclides emitting low radiation doses, such as the ones found at the Quinta do Bispo uranium mine, may pose a potential risk to human and environmental health and we should be alarmed about it. Considering this, the present study aims to evaluate the genotoxicity and mutagenicity of the effluent collected from the Quinta do Bispo uranium mine (Viseu, Portugal), in HepG2 cells exposed in vitro. The comet assay was employed to determine its potential to induce DNA damage and the mini-Ames assay (only with strains TA98 and TA100 of Salmonella typhimurium) to evaluate the potential for the induction of reverse mutations. The effluents ability to induce alterations in cell’s normal metabolism was also evaluated by proteomic analysis. The results showed that HepG2 cells exposed to the effluent presented significant DNA damage, i.e. the effluent at 18.8% was shown to be genotoxic. In the Ames test, the effluent was not considered a mutagen, since with none of the Salmonella typhimurium TA98 and TA100 strains, a mutagenicity ratio greater than or equal to 2 was obtained. In the proteomic analyses, 21522 proteins have been detected and 0.3% of them were found significantly deregulated. The over-regulated proteins with a higher abundance ratio are MDK, DKK4, DKK1 and ANG and the most under-regulated are TMEM165, AFP, STBD1 and THBS2, and may be potential biomarkers. In the context of this study, the two molecular functions that stood out were the ferroxidase activity (FTH1 and CP) and the ferric iron binding (FTL and FTH1), which are related with Ferroptosis. The study of these proteins may be essential for understanding the response mechanism involved. Indeed, the most represented were Ferroptosis, the Complement and coagulation cascades and the p53 signaling pathway as well as apoptosis, necroptosis and the wnt signaling pathway. Of the 66 differently expressed proteins, the eleven that are secreted and overexpressed may be interesting for future bystander effect studies. |
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| Autores principais: | Vieira, Leticia Isabel Rato |
| Assunto: | Uranium mining effluent Genotoxicity Mutagenicity Metals Radionuclides Low doses radiation Deregulated proteins |
| Ano: | 2021 |
| País: | Portugal |
| Tipo de documento: | dissertação de mestrado |
| Tipo de acesso: | acesso aberto |
| Instituição associada: | Universidade de Aveiro |
| Idioma: | inglês |
| Origem: | RIA - Repositório Institucional da Universidade de Aveiro |
| Resumo: | We are constantly exposed to ionizing radiation in different ways, through both natural or artificial sources, which one possible source is the uranium mining activity. However, the disposal of uranium mining tailings has resulted in their accumulation in the environment and the accidental exposure of human and nonhuman biota to several metals and radionuclides. Several impacts may result from this type of exposure, which can ultimately cause DNA damage and possibly mutations that can lead to carcinogenesis. Additionally, the interaction between metals and radionuclides may result in synergistic effects, and the response mechanisms underlying still need to be understood. Therefore, the exposure to complex environmental matrices containing a mixture of metals and radionuclides emitting low radiation doses, such as the ones found at the Quinta do Bispo uranium mine, may pose a potential risk to human and environmental health and we should be alarmed about it. Considering this, the present study aims to evaluate the genotoxicity and mutagenicity of the effluent collected from the Quinta do Bispo uranium mine (Viseu, Portugal), in HepG2 cells exposed in vitro. The comet assay was employed to determine its potential to induce DNA damage and the mini-Ames assay (only with strains TA98 and TA100 of Salmonella typhimurium) to evaluate the potential for the induction of reverse mutations. The effluents ability to induce alterations in cell’s normal metabolism was also evaluated by proteomic analysis. The results showed that HepG2 cells exposed to the effluent presented significant DNA damage, i.e. the effluent at 18.8% was shown to be genotoxic. In the Ames test, the effluent was not considered a mutagen, since with none of the Salmonella typhimurium TA98 and TA100 strains, a mutagenicity ratio greater than or equal to 2 was obtained. In the proteomic analyses, 21522 proteins have been detected and 0.3% of them were found significantly deregulated. The over-regulated proteins with a higher abundance ratio are MDK, DKK4, DKK1 and ANG and the most under-regulated are TMEM165, AFP, STBD1 and THBS2, and may be potential biomarkers. In the context of this study, the two molecular functions that stood out were the ferroxidase activity (FTH1 and CP) and the ferric iron binding (FTL and FTH1), which are related with Ferroptosis. The study of these proteins may be essential for understanding the response mechanism involved. Indeed, the most represented were Ferroptosis, the Complement and coagulation cascades and the p53 signaling pathway as well as apoptosis, necroptosis and the wnt signaling pathway. Of the 66 differently expressed proteins, the eleven that are secreted and overexpressed may be interesting for future bystander effect studies. |
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