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Prolonged exposure to particulate Cr(VI) is cytotoxic and genotoxic to fin whale cells
Affiliation:1. Wise Laboratory of Environmental and Genetic Toxicology, Department of Pharmacology and Toxicology, University of Louisville, 500 S Preston St, Rm 1422, Louisville, KY, United States;2. University of Southern Maine, Portland, ME, USA;1. School of Public Health, The Key Laboratory of Environmental Pollution Monitoring and Disease Control, Ministry of Education, Guizhou Medical University, Guiyang, 550025, China;2. Guizhou Orthopedics Hospital, Guiyang, 550007, China;1. Clinical Medical College, Dali University, Dali, Yunnan, China;2. Affiliated Hospital of Guizhou Medical University, Guiyang, China;3. Department of Oncology, Chongqing Hospital of Traditional Chinese Medicine, Chongqing, China;4. Xinqiao Hospital, Third Military Medical University (Army Medical University), Chongqing, China;1. School of Medicine, Universidad Panamericana, Mexico City, Mexico;2. Univerisidad de Papaloapan, Oaxaca, Mexico;3. Laboratory of Developmental Biology Research and Experimental Teratogenicity. Children’s Hospital of Mexico Federico Gomez (HIMFG), Mexico City, Mexico;1. Center for Basic Medical Research & Department of Cardiovascular Surgery, TEDA International Cardiovascular Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, China;2. Unit of Perfusion, Department of Cardiovascular Surgery, TEDA International Cardiovascular Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, China;3. Department of Cardiovascular Surgery, The First Affiliated Hospital, Zhejiang University, Hangzhou, China;4. School of Pharmacy, Wannan Medical College, Wuhu, China;5. Department of Surgery, Oregon Health and Science University, Portland, Oregon, USA;1. Istituto Zooprofilattico Sperimentale del Piemonte, Liguria e Valle d’Aosta, Torino, Italy;2. Department of Veterinary Medical Sciences, Alma Mater Studiorum, Università di Bologna, Ozzano dell’Emilia, BO, Italy;3. Istituto Zooprofilattico Sperimentale delle Venezie, Legnaro, PD, Italy;4. Laboratoire Frank Duncombe LABEO, Caen, France
Abstract:BackgroundHexavalent chromium [Cr(VI)] is a human lung carcinogen and global marine pollutant. High Cr concentrations, resembling the ones observed in occupationally exposed workers, have been observed in fin whales (Balaenoptera physalus) in the Gulf of Maine. This outcome suggests Cr might be disrupting the health of fin whale populations. Indeed, Cr in acute (24 h) exposure does cause toxicity in fin whale cells. However, human cell culture data indicate prolonged exposures (120 h) induce a higher amount of toxicity compared to 24 h exposure due to an inhibition of homologous recombination repair. However, whether prolonged exposure causes similar outcomes in fin whale cells is unknown.ObjectiveDue to the importance of assessing prolonged exposure toxicity, this study focuses on characterizing acute and prolonged exposure of Cr(VI) in male and female fin whale cells.MethodsCytotoxicity was measured by the clonogenic assay, also known as colony forming assay, which measures the ability of cells to proliferate and form colonies after the treatment. DNA double strand breaks were analyzed by neutral comet assay. Clastogenicity was measured using the chromosome aberration assay. Intracellular Cr levels were measured with Graphite Furnace Atomic Absorption Spectrometry (GFAAS) with Syngistix Software.ResultsIn this study, we demonstrate that particulate Cr(VI) induces cytotoxicity and genotoxicity in a treatment-dependent manner after 24 h and 120 h exposures. Cytotoxicity levels were generally low with relative survival above 64 %. DNA double strand break data and chromosome aberration data were elevated after a 24 h exposure, but decreased after a 120 h exposure. While cytotoxicity was similar after 24 h and 120 h exposures, less DNA double strand breaks and chromosomal instability occurred with prolonged exposure.ConclusionParticulate Cr(VI) is cytotoxic and genotoxic to fin whale cells after acute and prolonged exposures. The reduction of genotoxicity we have observed after 120 h exposure may be partly explained by lower intracellular Cr levels after 120 h. However, the decrease in intracellular levels is not reflected by a similar decrease in chromosome aberrations suggesting other mechanisms may be at play. Male fin whale cells appear to be more susceptible to the genotoxic effects of particulate Cr(VI) while female cells are less susceptible possibly due to increased cell death of damaged cells, but more work is needed to clarify if this outcome reflects a sex difference or interindividual variability. Overall, the study shows particulate Cr(VI) does induce toxicity at both acute and prolonged exposures in fin whales cells indicating Cr(VI) exposure is a health risk for this species.
Keywords:Metal  Particulate hexavalent chromium  Cytotoxicity  Genotoxicity  Fin whale  Chromosome instability
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