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Molecular and behavioral assessment in larval zebrafish (Danio rerio) following exposure to environmentally relevant levels of the antineoplastic cyclophosphamide.

Abstract
Antineoplastics treat cancers and enter aquatic ecosystems through wastewater and hospital effluent. Risks associated with antineoplastics are not well characterized in aquatic organisms. We conducted zebrafish embryo/larvae toxicity assays to evaluate responses to cyclophosphamide (0.01-50 µM). Zebrafish survival was affected by 5 µM cyclophosphamide and deformities were noted at > 1 µM. Oxidative respiration remained unchanged in embryos with exposure up to 200 µM. Reactive oxygen species were not increased by 50 µM cyclophosphamide exposure. More than 15 oxidative stress and immune-related transcripts were measured. Superoxide dismutase 2 and heat shock protein 70 and 90a were induced in larvae by cyclophosphamide. Immune-related transcripts were assessed due to immunosuppressive properties of cyclophosphamide, and mmp9 and myd88 levels were altered in expression. Hyperactivity of larvae was noted following 5 µM cyclophosphamide exposure. There was no change in anxiety-related endpoints (light-dark preference). Risks for larval fish exposed to cyclophosphamide in the environment may be low.
AuthorsEmma Ivantsova, Michelle Huang, Andrew S Wengrovitz, Christopher L Souders 2nd, Christopher J Martyniuk
JournalEnvironmental toxicology and pharmacology (Environ Toxicol Pharmacol) Vol. 90 Pg. 103809 (Feb 2022) ISSN: 1872-7077 [Electronic] Netherlands
PMID35033682 (Publication Type: Journal Article)
CopyrightCopyright © 2022 Elsevier B.V. All rights reserved.
Chemical References
  • Antineoplastic Agents
  • Water Pollutants, Chemical
  • Cyclophosphamide
Topics
  • Animals
  • Antineoplastic Agents (toxicity)
  • Behavior, Animal (drug effects)
  • Cyclophosphamide (toxicity)
  • Embryo, Nonmammalian (drug effects)
  • Gene Expression Regulation, Developmental (drug effects)
  • Larva (drug effects)
  • Mitochondria (metabolism)
  • Oxidative Stress (drug effects)
  • Water Pollutants, Chemical (toxicity)
  • Zebrafish (abnormalities, growth & development, physiology)

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