Cytosine arabinoside exposure induced cytotoxic effects and neural tube defects in mice and embryo stem cells

Autor: Zhen Guan, Yingchao Liang, Zhiqiang Zhu, Aiyun Yang, Shen Li, Jin Guo, Fang Wang, Huimin Yang, Na Zhang, Xiuwei Wang, Jianhua Wang
Jazyk: angličtina
Rok vydání: 2023
Předmět:
Zdroj: Ecotoxicology and Environmental Safety, Vol 262, Iss , Pp 115141- (2023)
Druh dokumentu: article
ISSN: 0147-6513
DOI: 10.1016/j.ecoenv.2023.115141
Popis: Cytosine arabinoside (Ara-C) is one of the most widely used chemotherapeutic agents for hematological malignancies. The residues of Ara-C have been detected in wastewater and river water with increased usage and discharge. As the ability to cross the placenta and the teratogenicity at low ng/L levels, the toxic effects on pregnant women and infants have been concerned. The toxicity of Ara-C exposure on early embryonic neurodevelopment has not been fully elucidated. In this study, pregnant C57BL/6 mice were injected with different doses of Ara-C on Gestation day (GD) 7.5 and assessed on GD11.5 and GD13.5 to explore the neural developmental effects of Ara-C. HE staining, immunofluorescence, western blot, EdU assay, and flow cytometry were utilized to determine the toxic effects of Ara-C in vivo and in vitro. Our results showed that Ara-C (15–22.5 mg/kg body weight) induced the occurrence of neural tube defects (NTDs). The expression of PH3 was markedly reduced in embryos with Ara-C-induced NTDs, compared to the control group (P
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