PUBLICATION
Thallium(I) induces a prolonged inhibition of (6-4)photoproduct binding and UV damage excision repair activities in zebrafish (Danio rerio) embryos via protein inactivation
- Authors
- Huang, Y.Y., Paul, G.V., Hsu, T.
- ID
- ZDB-PUB-231218-14
- Date
- 2023
- Source
- Chemico-biological interactions 388: 110837 (Journal)
- Registered Authors
- Hsu, Todd
- Keywords
- 6-4 photoproduct, Thallium, UV, Zebrafish
- MeSH Terms
-
- Animals
- DNA Damage
- DNA Repair
- Excision Repair*
- Humans
- Pyrimidine Dimers/metabolism
- Thallium/metabolism
- Thallium/toxicity
- Ultraviolet Rays
- Zebrafish*/metabolism
- PubMed
- 38104746 Full text @ Chem. Biol. Interact.
Citation
Huang, Y.Y., Paul, G.V., Hsu, T. (2023) Thallium(I) induces a prolonged inhibition of (6-4)photoproduct binding and UV damage excision repair activities in zebrafish (Danio rerio) embryos via protein inactivation. Chemico-biological interactions. 388:110837.
Abstract
Cyclobutane pyrimidine dimer (CPD) and (6-4)photoproduct (6-4PP) are two major types of UV-induced DNA lesion and 6-4PP is more mutagenic than CPD. Activated by lesion detection, nucleotide excision repair (NER) eliminates CPDs and 6-4PPs. Thallium (Tl) is a toxic metal existing primarily as Tl+ in the aquatic environment. Ingestion of Tl+-contaminated foods and water is a major route of human poisoning. As Tl+ may inhibit enzyme activities via binding to sulfhydryl groups, this study explored if Tl+ could intensify UV mutagenicity by inactivating NER-linked damage recognition factors using zebrafish (Danio rerio) embryo as a model system. Incubation of Tl+ (as thallium nitrate) at 0.1-0.4μg/mL with zebrafish extracts for 20 min caused a concentration-dependent inhibition of 6-4PP binding activities as shown by a photolesion-specific band shift assay, while CPD binding activities were insensitive to Tl+. The ability of Tl+ to suppress 6-4PP detection was stronger than that of Hg2+. Exposure of zebrafish embryos at 1 h post fertilization (hpf) to Tl+ at 0.4-1μg/mL for 9 or 71 h also specifically inhibited 6-4PP detection, indicating that Tl+ induced a prolonged inhibition of 6-4PP sensing ability primarily via its direct interaction with damage recognition molecules. Tl+-mediated inhibition of 6-4PP binding in embryos at distinct stages resulted in a suppression of NER capacity monitored by a transcription-based DNA repair assay. Our results revealed the potential of Tl+ to enhance UV mutagenicity by disturbing the removal of 6-4PP through repressing the lesion detection step of NER.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping