Prednisone is genotoxic in mice and Drosophila melanogaster

•Prednisone showed potent genotoxic action in mouse bone marrow micronucleus test.•Prednisone demonstrated high genotoxic effect in comet assay in mice bone marrow cells.•Prednisone showed potent genotoxic action in D. melanogaster in SMART test.•Somatic recombination was the main genotoxic effect observed in SMART test.•Histopathological analysis showed no relevant toxicity of prednisone in mice tissues. Prednisone (PD) is one of the most commonly used corticosteroids in immunosuppressive therapy for patients with autoimmune diseases and transplants. Chronic use of corticosteroids is associated with several side effects and an increase in neoplasia. Since genotoxic effects are associated with an increased risk of cancer development, this study evaluated the genotoxic and cytotoxic activities of PD using the SMART/wing assay in Drosophila melanogaster and the micronucleus test and comet assay in mouse bone marrow cells. Further, the toxic effects of PD on mouse organ tissues were assessed using histopathological analyses. In the SMART/wing assay, PD showed a significant genotoxic activity at all concentrations tested (0.375, 0.75, 1.5, and 2.0 mg/mL) compared to the negative control (p < 0.05). The micronucleus test and comet assay also showed an elevated genotoxicity of PD at all treatment conditions (24, 48, and 120 h with doses ranging from 0.5 to 1.5 mg/kg) compared to the negative control (p < 0.05). The histopathological analyses did not show toxicity of PD in mouse cells and tissues. Therefore, our results demonstrate that PD is a potent genotoxic immunosuppressant in mice and D. melanogaster cells. Somatic recombination was the primary contributor (46%–82%) to the induced genotoxicity observed in the SMART test.