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Pharmacogenet Genomics. 2012 Apr;22(4):285-9. doi: 10.1097/FPC.0b013e3283514395.

Chemotherapy-induced toxicity is highly heritable in Drosophila melanogaster.

Author information

1
Department of Ecology and Evolution, University of California, Irvine, California, USA. gdvorkin@uci.edu

Abstract

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.

PMID:
22336958
PMCID:
PMC3303944
DOI:
10.1097/FPC.0b013e3283514395
[Indexed for MEDLINE]
Free PMC Article
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