PUBLICATION
DNA Damage Response Is Involved in the Developmental Toxicity of Mebendazole in Zebrafish Retina
- Authors
- Sasagawa, S., Nishimura, Y., Kon, T., Yamanaka, Y., Murakami, S., Ashikawa, Y., Yuge, M., Okabe, S., Kawaguchi, K., Kawase, R., Tanaka, T.
- ID
- ZDB-PUB-160326-5
- Date
- 2016
- Source
- Frontiers in pharmacology 7: 57 (Journal)
- Registered Authors
- Tanaka, Toshio
- Keywords
- ATM, DNA damage response, benzimidazole, developmental toxicity, systems toxicology, zebrafish
- Datasets
- GEO:GSE75245
- MeSH Terms
- none
- PubMed
- 27014071 Full text @ Front Pharmacol
Citation
Sasagawa, S., Nishimura, Y., Kon, T., Yamanaka, Y., Murakami, S., Ashikawa, Y., Yuge, M., Okabe, S., Kawaguchi, K., Kawase, R., Tanaka, T. (2016) DNA Damage Response Is Involved in the Developmental Toxicity of Mebendazole in Zebrafish Retina. Frontiers in pharmacology. 7:57.
Abstract
Intestinal helminths cause iron-deficiency anemia in pregnant women, associated with premature delivery, low birth weight, maternal ill health, and maternal death. Although benzimidazole compounds such as mebendazole (MBZ) are highly efficacious against helminths, there are limited data on its use during pregnancy. In this study, we performed in vivo imaging of the retinas of zebrafish larvae exposed to MBZ, and found that exposure to MBZ during 2 and 3 days post-fertilization caused malformation of the retinal layers. To identify the molecular mechanism underlying the developmental toxicity of MBZ, we performed transcriptome analysis of zebrafish eyes. The analysis revealed that the DNA damage response was involved in the developmental toxicity of MBZ. We were also able to demonstrate that inhibition of ATM significantly attenuated the apoptosis induced by MBZ in the zebrafish retina. These results suggest that MBZ causes developmental toxicity in the zebrafish retina at least partly by activating the DNA damage response, including ATM signaling, providing a potential adverse outcome pathway in the developmental toxicity of MBZ in mammals.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping