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Teratogenic effects of five anticancer drugs on Xenopus laevis embryos
Marina Isidori1, Concetta Piscitelli1, Chiara Russo1
1Dipartimento di Scienze e Tecnologie Ambientali, Biologiche e Farmaceutiche, Seconda Università di Napoli, Via Vivaldi 43, I-81100 Caserta, Italy.
Abstract:
In recent years, the environmental presence of pharmaceuticals - including anticancer drugs - is an emerging issue. Because of the lack of appropriate critical studies about anticancer drug effects in frogs, the aim of the present study was to investigate lethal and teratogenic effects of five anticancer drugs widely used in large quantities, i.e. 5-flourouracil, capecitabine, cisplatin, etoposide, and imatinib, in the embryos of the South African clawed frog, Xenopus laevis, using FETAX - Frog Embryo Teratogenesis Assay in Xenopus. None of the studied anticancer drugs induced statistically significant mortality within the concentrations tested (0.01-50mg/L, depending on the studied compound), and no growth inhibition of embryos after a 96-h exposure was observed. Except for cisplatin, the other pharmaceuticals induced an increase of developmental malformations such as abdominal edema, axial flexure, head, eyes, gut and heart malformations with statistically significant effects observed at the highest concentrations tested (50mg/L for 5-flourouracil; 30mg/L for etoposide and 20mg/L for capecitabine and imatinib). The results indicate that anticancer drugs can affect embryogenesis mechanisms.
Insights
Five common anticancer drugs did not cause mortality in frog embryos but did increase developmental malformations. This study highlights potential risks of anticancer pharmaceuticals to aquatic embryogenesis.
Area of Science:
- Environmental Science
- Toxicology
- Developmental Biology
Background:
- Pharmaceuticals, including anticancer drugs, are increasingly detected in the environment.
- There is a lack of comprehensive studies on the ecotoxicological effects of anticancer agents on amphibians.
Purpose of the Study:
- To investigate the lethal and teratogenic effects of five widely used anticancer drugs on Xenopus laevis embryos.
- To assess the impact of 5-fluorouracil, capecitabine, cisplatin, etoposide, and imatinib on early frog development.
Main Methods:
- Utilized the Frog Embryo Teratogenesis Assay in Xenopus (FETAX) for testing.
- Exposed Xenopus laevis embryos to varying concentrations of five anticancer drugs over 96 hours.
- Monitored for mortality, growth inhibition, and specific developmental malformations.
Main Results:
- No statistically significant mortality or growth inhibition was observed for any of the tested anticancer drugs.
- Cisplatin did not induce significant teratogenic effects.
- 5-fluorouracil, capecitabine, etoposide, and imatinib caused statistically significant increases in developmental malformations, including abdominal edema and organ defects, at higher concentrations.
Conclusions:
- Anticancer drugs, excluding cisplatin, can significantly impact embryogenesis mechanisms in Xenopus laevis.
- Environmental exposure to these pharmaceuticals may pose a risk to aquatic vertebrate development.
