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Updated: May 24, 2026
Assessment of Chemical Toxicity in Adult Drosophila Melanogaster
Published on: March 24, 2023
Chemotherapy-induced toxicity is highly heritable in Drosophila melanogaster
Galina Kislukhin1, Maura L Murphy, Mahtab Jafari
1Department of Ecology and Evolution, University of California, Irvine, California, USA. gdvorkin@uci.edu
Objectives:
Identification of the genes responsible for chemotherapy toxicity in Drosophila melanogaster may allow for the identification of human orthologs that similarly mediate toxicity in humans. To develop D. melanogaster as a model of dissecting chemotoxicity, we first need to develop standardized high-throughput toxicity assays and prove that the interindividual variation in toxicity as measured by such assays is highly heritable.
Methods:
We developed a method for the oral delivery of commonly used chemotherapy drugs to Drosophila. Post-treatment female fecundity displayed a dose-dependent response to varying levels of the chemotherapy drug delivered. We fixed the dose for each drug at a level that resulted in a 50% reduction in fecundity and used a paternal half-sibling heritability design to calculate the heritability attributable to chemotherapy toxicity assayed by a decrease in female fecundity. The chemotherapy agents tested were carboplatin, floxuridine, gemcitabine hydrochloride, methotrexate, mitomycin C, and topotecan hydrochloride.
Results:
We found that six currently widely prescribed chemotherapeutic agents lowered fecundity in D. melanogaster in both a dose-dependent and a highly heritable manner. The following heritability estimates were found: carboplatin, 0.72; floxuridine, 0.52; gemcitabine hydrochloride, 0.72; methotrexate, 0.99; mitomycin C, 0.64; and topotecan hydrochloride, 0.63.
Conclusion:
The high heritability estimates observed in this study, irrespective of the particular class of drug examined, suggest that human toxicity may also have a sizable genetic component.
Insights
Chemotherapy drugs significantly reduce fruit fly fecundity in a heritable manner. This suggests that genetic factors play a substantial role in chemotherapy toxicity in humans.
Area of Science:
- Genetics
- Toxicology
- Model Organisms
Background:
- Chemotherapy toxicity varies significantly among individuals.
- Identifying genetic factors underlying this toxicity is crucial for personalized medicine.
- Drosophila melanogaster offers a powerful model for genetic studies.
Purpose of the Study:
- To develop standardized assays for high-throughput chemotoxicity screening in Drosophila.
- To establish Drosophila as a model for dissecting the genetic basis of chemotherapy toxicity.
- To assess the heritability of chemotherapy-induced toxicity in Drosophila.
Main Methods:
- Developed oral drug delivery for six chemotherapy agents in Drosophila.
- Assayed toxicity by measuring female fecundity reduction post-treatment.
- Utilized a paternal half-sibling heritability design to quantify genetic contributions.
Main Results:
- Six chemotherapy drugs (carboplatin, floxuridine, gemcitabine hydrochloride, methotrexate, mitomycin C, topotecan hydrochloride) reduced Drosophila fecundity.
- Toxicity exhibited a dose-dependent response.
- High heritability estimates for toxicity were observed, ranging from 0.52 to 0.99.
Conclusions:
- Chemotherapy toxicity in Drosophila is highly heritable.
- These findings suggest a significant genetic component to chemotherapy toxicity in humans.
- Drosophila serves as a valuable model for future genetic investigations into chemotoxicity.
