Aluminum (Al) causes a delayed suppression of nucleotide excision repair (NER) capacity in zebrafish (Danio rerio) embryos via disturbance of DNA lesion detection
Aluminum (Al) is extensively used for making cooking utensils and its presence in the aquatic environment may occur through acid mine drainage and wastewater discharge. Al is known to induce genotoxicity in human cells, rodents, and fish. Nucleotide excision repair (NER) eliminates helix-twisting DN...
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| Format: | Article |
| Language: | English |
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Elsevier
2022-09-01
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| Series: | Ecotoxicology and Environmental Safety |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S0147651322007424 |
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| author | Ganjai Vikram Paul Ya-Yun Huang Yu-Ning Wu Tsung-Nan Ho Hsin-I. Hsiao Todd Hsu |
| author_facet | Ganjai Vikram Paul Ya-Yun Huang Yu-Ning Wu Tsung-Nan Ho Hsin-I. Hsiao Todd Hsu |
| author_sort | Ganjai Vikram Paul |
| collection | DOAJ |
| description | Aluminum (Al) is extensively used for making cooking utensils and its presence in the aquatic environment may occur through acid mine drainage and wastewater discharge. Al is known to induce genotoxicity in human cells, rodents, and fish. Nucleotide excision repair (NER) eliminates helix-twisting DNA lesions such as UV-induced dipyrimidine photoproducts. Because our earlier investigation revealed the operation of NER in zebrafish (Danio rerio) embryos, this study explored if inhibition of NER could be a mechanism of Al-induced genotoxicity using zebrafish embryo as a model system. An acute fish embryo toxicity test indicated that Al (as aluminum sulfate) at 2–15 mg/L were nonlethal to zebrafish embryos, yet exposure of embryos at 1 h post fertilization (hpf) to Al at 10–15 mg/L for 71 h significantly repressed their NER capacity monitored by a transcription-based DNA repair assay. Band shift analysis indicated a higher sensitivity of (6−4) photoproduct (6–4PP) than cyclobutane pyrimidine dimer (CPD) detecting activities to Al, reflecting the preferential influence of Al on the detection of strongly distorted DNA lesions. Time-course experiments showed a delayed response of NER to Al as repair machinery was unaffected by Al at 15 mg/L following a 35-h exposure, while Al treatment for the same period obviously inhibited 6–4PP binding activities although the gene expression of damage recognition factors remained active. Inhibition of 6–4PP detection blocked downstream lesion incision/excision detected by a terminal deoxy transferase-mediated end labeling assay. As the disturbance of damage sensing preceded that of the overall repair process, Al exposure was believed to downregulate NER capacity by inhibiting the activities of lesion detection proteins. Our results revealed the ability of Al to enhance its genotoxicity by suppressing NER capacity. |
| first_indexed | 2024-12-10T16:29:07Z |
| format | Article |
| id | doaj.art-7ae0eb64fc6342d3bf170d0d7be45123 |
| institution | Directory Open Access Journal |
| issn | 0147-6513 |
| language | English |
| last_indexed | 2024-12-10T16:29:07Z |
| publishDate | 2022-09-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Ecotoxicology and Environmental Safety |
| spelling | doaj.art-7ae0eb64fc6342d3bf170d0d7be451232022-12-22T01:41:34ZengElsevierEcotoxicology and Environmental Safety0147-65132022-09-01242113902Aluminum (Al) causes a delayed suppression of nucleotide excision repair (NER) capacity in zebrafish (Danio rerio) embryos via disturbance of DNA lesion detectionGanjai Vikram Paul0Ya-Yun Huang1Yu-Ning Wu2Tsung-Nan Ho3Hsin-I. Hsiao4Todd Hsu5Department of Bioscience and Biotechnology and Center of Excellence for the Oceans, National Taiwan Ocean University, Keelung 202301, TaiwanDepartment of Bioscience and Biotechnology and Center of Excellence for the Oceans, National Taiwan Ocean University, Keelung 202301, TaiwanGraduate Institute of Food Safety and Risk Management, National Taiwan Ocean University, Keelung, 202301, TaiwanDepartment of Bioscience and Biotechnology and Center of Excellence for the Oceans, National Taiwan Ocean University, Keelung 202301, TaiwanGraduate Institute of Food Safety and Risk Management, National Taiwan Ocean University, Keelung, 202301, Taiwan; Department of Food Science, National Taiwan Ocean, University, Keelung, 202301, TaiwanDepartment of Bioscience and Biotechnology and Center of Excellence for the Oceans, National Taiwan Ocean University, Keelung 202301, Taiwan; Corresponding author.Aluminum (Al) is extensively used for making cooking utensils and its presence in the aquatic environment may occur through acid mine drainage and wastewater discharge. Al is known to induce genotoxicity in human cells, rodents, and fish. Nucleotide excision repair (NER) eliminates helix-twisting DNA lesions such as UV-induced dipyrimidine photoproducts. Because our earlier investigation revealed the operation of NER in zebrafish (Danio rerio) embryos, this study explored if inhibition of NER could be a mechanism of Al-induced genotoxicity using zebrafish embryo as a model system. An acute fish embryo toxicity test indicated that Al (as aluminum sulfate) at 2–15 mg/L were nonlethal to zebrafish embryos, yet exposure of embryos at 1 h post fertilization (hpf) to Al at 10–15 mg/L for 71 h significantly repressed their NER capacity monitored by a transcription-based DNA repair assay. Band shift analysis indicated a higher sensitivity of (6−4) photoproduct (6–4PP) than cyclobutane pyrimidine dimer (CPD) detecting activities to Al, reflecting the preferential influence of Al on the detection of strongly distorted DNA lesions. Time-course experiments showed a delayed response of NER to Al as repair machinery was unaffected by Al at 15 mg/L following a 35-h exposure, while Al treatment for the same period obviously inhibited 6–4PP binding activities although the gene expression of damage recognition factors remained active. Inhibition of 6–4PP detection blocked downstream lesion incision/excision detected by a terminal deoxy transferase-mediated end labeling assay. As the disturbance of damage sensing preceded that of the overall repair process, Al exposure was believed to downregulate NER capacity by inhibiting the activities of lesion detection proteins. Our results revealed the ability of Al to enhance its genotoxicity by suppressing NER capacity.http://www.sciencedirect.com/science/article/pii/S0147651322007424AluminumNucleotide excision repairDipyrimidine photoproductsUVZebrafish |
| spellingShingle | Ganjai Vikram Paul Ya-Yun Huang Yu-Ning Wu Tsung-Nan Ho Hsin-I. Hsiao Todd Hsu Aluminum (Al) causes a delayed suppression of nucleotide excision repair (NER) capacity in zebrafish (Danio rerio) embryos via disturbance of DNA lesion detection Ecotoxicology and Environmental Safety Aluminum Nucleotide excision repair Dipyrimidine photoproducts UV Zebrafish |
| title | Aluminum (Al) causes a delayed suppression of nucleotide excision repair (NER) capacity in zebrafish (Danio rerio) embryos via disturbance of DNA lesion detection |
| title_full | Aluminum (Al) causes a delayed suppression of nucleotide excision repair (NER) capacity in zebrafish (Danio rerio) embryos via disturbance of DNA lesion detection |
| title_fullStr | Aluminum (Al) causes a delayed suppression of nucleotide excision repair (NER) capacity in zebrafish (Danio rerio) embryos via disturbance of DNA lesion detection |
| title_full_unstemmed | Aluminum (Al) causes a delayed suppression of nucleotide excision repair (NER) capacity in zebrafish (Danio rerio) embryos via disturbance of DNA lesion detection |
| title_short | Aluminum (Al) causes a delayed suppression of nucleotide excision repair (NER) capacity in zebrafish (Danio rerio) embryos via disturbance of DNA lesion detection |
| title_sort | aluminum al causes a delayed suppression of nucleotide excision repair ner capacity in zebrafish danio rerio embryos via disturbance of dna lesion detection |
| topic | Aluminum Nucleotide excision repair Dipyrimidine photoproducts UV Zebrafish |
| url | http://www.sciencedirect.com/science/article/pii/S0147651322007424 |
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