Toxicogenomics of Five Cytostatics in Fathead Minnow (Pimephales promelas) Larvae.

In this study, the toxicogenomic effects of five cytostatics (tamoxifen, methotrexate, capecitabine, cyclophosphamide, and ifosfamide) on fathead minnow (Pimephales promelas) larvae were evaluated. Post-fertilization eggs were exposed to increasing concentrations of the drugs for six days. The expression levels of two genetic biomarkers for toxicity and four thyroid hormone-related gene pathways were measured. Interestingly, the results showed that all concentrations of the five cytostatics affect the transcription levels of both toxicity biomarker genes. Additionally, the thyroid hormone-related genes had different expression levels than the control, with the most significant changes observed in those larvae exposed to cyclophosphamide and ifosfamide. While a previous study found no effects on fish morphology, this study suggests that the five cytostatics modify subtle molecular responses of P. promelas, highlighting the importance of assessing multibiological level endpoints throughout the lifecycle of animals to understand the full portrait of potential effects of cytostatics and other contaminants.

Embryotoxicity of Five Cytostatics in Fathead Minnow (Pimephales promelas) Larvae.

Cytostatics are compounds used in chemotherapy, known to be genotoxic, mutagenic, and teratogenic at low concentrations. The amount of cytostatic drugs prescribed increases every year as does their release into the aquatic ecosystems, which possibly is a major concern for the health of aquatic organisms. This study aimed to evaluate the putative toxicity of five cytostatics to fathead minnow (Pimephales promelas) larvae: tamoxifen, capecitabine, methotrexate, cyclophosphamide, and ifosfamide. Eggs collected post-fertilization were exposed for 6 days to a range of concentrations, including one above environmental level. At all environmental concentrations, no significant difference in mortality, hatching time, length, heart rate, and presence of malformations were found. Altogether, these cytostatics do not seem embryotoxic to fish. Although, an increased proportion of complete swim bladder were found after ifosfamide's exposure, suggesting an interaction with the thyroid axis, involved in swim bladder development. Complementary work should address other endpoints, such as behavioral changes, reproductive success, and transgenerational effects.