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.

Cyclobutane pyrimidine dimer (CPD) and (6-4)photoproduct (6-4 PP) are two major types of UV-induced DNA lesion and 6-4 PP is more mutagenic than CPD. Activated by lesion detection, nucleotide excision repair (NER) eliminates CPDs and 6-4 PPs. 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 0.1-0.4 μg/mL with zebrafish extracts for 20 min caused a concentration-dependent inhibition of 6-4 PP 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 6-4 PP detection was stronger than that of Hg ²⁺ . Exposure of zebrafish embryos at 1 h post fertilization (hpf) to Tl ⁺ at 0.4-1 μg/mL for 9 or 71 h also specifically inhibited 6-4 PP detection, indicating that Tl ⁺ induced a prolonged inhibition of 6-4 PP sensing ability primarily via its direct interaction with damage recognition molecules. Tl ⁺ -mediated inhibition of 6-4 PP 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 6-4 PP through repressing the lesion detection step of NER.
Competing Interests: Declaration of competing interest The authors declare that there are no competing interests that could have appeared to influence the work reported in this article.
(Copyright © 2023 Elsevier B.V. All rights reserved.)