Drosophila strain specific response to cisplatin neurotoxicity

Fly (Austin). 2018;12(3-4):174-182. doi: 10.1080/19336934.2019.1565257. Epub 2019 Jan 22.

Abstract

Drosophila melanogaster has recently been developed as a simple, in vivo, genetic model of chemotherapy-induced peripheral neuropathy. Flies treated with the chemotherapy agent cisplatin display both a neurodegenerative phenotype and cell death in rapidly dividing follicles, mimicking the cell specific responses seen in humans. Cisplatin induces climbing deficiencies and loss of fertility in a dose dependent manner. Drosophila sensitivity to cisplatin in both cell types is affected by genetic background. We show that mutation or RNAi-based knockdown of genes known to be associated with CIPN incidence in humans affect sensitivity of flies to CIPN. Drosophila is a promising model with which to study the effect of genetics on sensitivity to CIPN.

Keywords: ABC transporter; Drosophila; chemotherapy-induced peripheral neuropathy; cisplatin; glutathione; neurodegeneration.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / toxicity*
  • Cisplatin / toxicity*
  • Disease Models, Animal
  • Drosophila / classification
  • Drosophila / drug effects*
  • Neurotoxicity Syndromes / etiology
  • Neurotoxicity Syndromes / pathology*
  • Neurotoxins / toxicity*
  • Peripheral Nervous System Diseases / chemically induced
  • Peripheral Nervous System Diseases / pathology*
  • Toxicity Tests

Substances

  • Antineoplastic Agents
  • Neurotoxins
  • Cisplatin