Vincristine exposure impairs skin keratinocytes, ionocytes, and lateral-line hair cells in developing zebrafish embryos

Abstract

Environmental contamination by anticancer pharmaceuticals has been widely reported. These drugs are not readily biodegradable, and their parent compounds and/or metabolites have been detected in surface waters and groundwater throughout the world. Adverse effects of anticancer drugs occur frequently in cancer patients, and a large body of clinical knowledge has accumulated. However, the effects of these drugs on aquatic organisms have not been thoroughly studied. This study aimed to investigate the effects of acute exposure to a common anticancer drug, vincristine (VCR), on zebrafish embryonic development and skin function. After 96 h of VCR exposure (0, 1, 10, 15, and 25 mg/L), significant teratogenic effects were observed, including growth retardation, pericardial edema, spine, tail, and yolk sac malformations (VCR ≥ 15 mg/L), a decreased heart rate, and ocular malformations (VCR ≥ 10 mg/L). The value of the half lethal concentration for zebrafish embryos was 20.6 mg/L. At ≥10 mg/L VCR, systemic ion contents and acid secretion in the skin over the yolk-sac decreased, and these findings were associated with decreases in skin ionocytes (H+-ATPase-rich cells and Na+-K+-ATPase-rich cells). Also, the microridge-structure of skin keratinocytes was significantly damaged. The number of lateral line hair cells was reduced when VCR was ≥10 mg/L, and functional impairment was detected when VCR was as low as 1 mg/L. Results of this in vivo study in zebrafish embryos indicate that acute exposure to VCR can lead to developmental defects, impairment of skin functions, and even fish death.