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

Drosophila strain specific response to cisplatin neurotoxicity

Christopher M Groen  1 , Jewel L Podratz  1 , Kevin Treb  2 , Anthony J Windebank  1
Affiliations

Drosophila strain specific response to cisplatin neurotoxicity

Christopher M Groen et al. Fly (Austin). 2018.

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.

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Figures

Figure 1.
Figure 1.
Wild-type strains have different sensitivity to cisplatin. a. Graph displaying the average percent of flies able to climb over a height of 2 cm in an automated climbing assay. b. Graph showing the percent survival of the flies tested in a. c. Graph quantifying fertility of female flies, displayed as the number of progeny per female, normalized to untreated controls for each genotype. d. Graph of the average ng of platinum per mg of total DNA isolated from flies of the indicated genotypes treated with control media or 75 ug/mL cisplatin. Wild-type strains have different sensitivity to dose-dependent climbing deficiencies (a), lethality (b), and fertility defects (c), despite acquiring the same levels of Pt-DNA adducts (d). *p < .05, **p < .01.
Figure 2.
Figure 2.
Eye color mutants have increased sensitivity to cisplatin. a,c. Climbing assay results for flies of the indicated genotypes and cisplatin treatments. b,d. Graph of the percent survival for flies analyzed in the climbing assay in panels a and c, respectively. White mutant flies (w1118 and y1w1) and brown (bw1) mutant flies are more sensitive to cisplatin-induced climbing deficiencies, while vermillion (v1) mutant flies are less sensitive to cisplatin-induced climbing deficiencies. Knockdown of white via RNAi also causes increased sensitivity to cisplatin-induced climbing deficiencies (c). *p < .05, **p < .01.
Figure 3.
Figure 3.
Knockdown of glutathione peroxidase affects cisplatin sensitivity. a. Climbing assay results for flies of the indicated genotypes and cisplatin treatments. b. Graph of the percent survival for flies analyzed in the climbing assay in panel a. c. Graph displaying fertility of female flies of the indicated genotypes and cisplatin treatments. Fertility is displayed the number of progeny per female, normalized to untreated controls for each genotype. Knockdown of glutathione peroxidase via RNAi causes increased sensitivity to cisplatin-induced climbing deficiencies (a) and fertility defects (b). **p < .01.
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