PUBLICATION
Mercury (II) impairs nucleotide excision repair (NER) in zebrafish (Danio rerio) embryos by targeting primarily at the stage of DNA incision
- Authors
- Chang, Y., Lee, W.Y., Lin, Y.J., Hsu, T.
- ID
- ZDB-PUB-170925-2
- Date
- 2017
- Source
- Aquatic toxicology (Amsterdam, Netherlands) 192: 97-104 (Journal)
- Registered Authors
- Hsu, Todd
- Keywords
- Embryo, Mercury, Nucleotide excision repair, Uv, Zebrafish
- MeSH Terms
-
- Adenosine Triphosphate/biosynthesis
- Animals
- DNA/metabolism
- DNA Damage*
- DNA Repair/drug effects*
- DNA Repair/radiation effects
- Embryo, Nonmammalian/drug effects*
- Embryo, Nonmammalian/metabolism*
- Embryo, Nonmammalian/radiation effects
- Gene Expression Regulation, Developmental/drug effects
- Mercuric Chloride/metabolism
- Mercury/toxicity*
- Pyrimidine Dimers/metabolism
- Ultraviolet Rays
- Water Pollutants, Chemical/toxicity
- Zebrafish/embryology*
- Zebrafish/genetics
- Zebrafish/metabolism*
- Zebrafish Proteins/genetics
- Zebrafish Proteins/metabolism
- PubMed
- 28942072 Full text @ Aquat. Toxicol.
Citation
Chang, Y., Lee, W.Y., Lin, Y.J., Hsu, T. (2017) Mercury (II) impairs nucleotide excision repair (NER) in zebrafish (Danio rerio) embryos by targeting primarily at the stage of DNA incision. Aquatic toxicology (Amsterdam, Netherlands). 192:97-104.
Abstract
Mercuric ion (Hg2+) is the most prevalent form of inorganic Hg found in polluted aquatic environment. As inhibition of DNA damage repair has been proposed as one of the mechanisms of Hg2+-induced genotoxicity in aquatic animals and mammalian cells, this study explored the susceptibility of different stages of nucleotide excision repair (NER) in zebrafish (Danio rerio) embryos to Hg2+ using UV-damaged DNA as the repair substrate. Exposure of embryos at 1h post fertilization (hpf) to HgCl2 at 0.1-2.5μM for 9h caused a concentration-dependent inhibition of NER capacity monitored by a transcription-based DNA repair assay. The extracts of embryos exposed to 2.5μM Hg2+ almost failed to up-regulate UV-suppressed marker cDNA transcription. No inhibition of ATP production was observed in all Hg2+-exposed embryos. Hg2+ exposure imposed either weak inhibitory or stimulating effects on the gene expression of NER factors, while band shift assay showed the inhibition of photolesion binding activities to about 40% of control in embryos treated with 1-2.5μM HgCl2. The damage incision stage of NER in zebrafish embryos was found to be more sensitive to Hg2+ than photolesion binding capacity due to the complete loss of damage incision activity in the extracts of embryos exposed to 1-2.5μM Hg2+. NER-related DNA incision was induced in UV-irradiated embryos based on the production of short DNA fragments matching the sizes of excision products generated by eukaryotic NER. Pre-exposure of embryos to Hg2+ at 0.1-2.5μM all suppressed DNA incision/excision in UV-irradiated embryos, reflecting a high sensitivity of DNA damage incision/excision to Hg2+. Our results showed the potential of Hg2+ at environmental relevant levels to disturb NER in zebrafish embryos by targeting primarily at the stage of DNA incision/excision.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping