Avaliação carcinogênica da fluoxetina em células epiteliais de D. melanogaster

Abstract

Depression is a growing public health issue, and fluoxetine is the most widely prescribed antidepressant. Despite its extensive use, data regarding its high-dose genotoxicity remains scarce and divergent. This study evaluated the toxicity and carcinogenic potential of different fluoxetine concentrations in epithelial cells of Drosophila melanogaster. The methodology utilized a survival assay with third-instar larvae under chronic treatment with fluoxetine (0.125 to 2 mg/mL). Carcinogenicity was assessed through the Epithelial Tumor Detection Test, using trans-heterozygous progeny for the warts tumor suppressor gene (mwh+/+wts). Data were statistically evaluated using the Chi-square test. Toxicity results demonstrated that survival is inversely proportional to concentration, as only the 2 mg/mL dose significantly reduced survival (40%) compared to the negative control (85%). In the tumor assay, concentrations up to 1 mg/mL showed no significant differences from the control, indicating a lack of carcinogenicity at low doses. However, the 2 mg/mL concentration caused a statistically significant increase in tumor induction, yielding 80 tumors across 41 flies. In conclusion, fluoxetine exhibits a strictly dose-dependent toxicogenic profile. The carcinogenic effect at 2 mg/mL does not result from direct DNA interaction, but rather from severe oxidative stress triggered by mitochondrial dysfunction and intracellular calcium dysregulation, which overwhelm cellular repair systems and induce apoptosis.