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Prednisone is genotoxic in mice and Drosophila melanogaster
Mutation Research/Genetic Toxicology and Environmental Mutagenesis ( IF 1.9 ) Pub Date : 2021-02-14 , DOI: 10.1016/j.mrgentox.2021.503334
Laís Camargo de Oliveira 1 , Abel Vieira de Melo Bisneto 1 , Sara Cristina Puga 1 , Amanda Silva Fernandes 1 , Jefferson Hollanda Véras 1 , Clever Gomes Cardoso 2 , Carolina Ribeiro E Silva 3 , Cristiene Costa Carneiro 4 , Lee Chen-Chen 1
Affiliation  

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.



中文翻译:

泼尼松对小鼠和黑腹果蝇具有遗传毒性

泼尼松(PD)是自身免疫性疾病和移植患者免疫抑制治疗中最常用的皮质类固醇之一。长期使用皮质类固醇与多种副作用和瘤形成增加有关。由于基因毒性作用与癌症发展风险增加有关,因此本研究使用黑腹果蝇中的 SMART/wing试验和小鼠骨髓细胞中的微核试验和彗星试验评估了 PD 的基因毒性和细胞毒性活性。此外,使用组织病理学分析评估了 PD 对小鼠器官组织的毒性作用。在 SMART/wing 试验中,与阴性对照相比,PD 在所有测试浓度(0.375、0.75、1.5 和 2.0 mg/mL)下均显示出显着的基因毒性活性(p< 0.05)。与阴性对照相比,微核试验和彗星试验还显示,在所有治疗条件下(24、48 和 120 小时,剂量范围为 0.5 至 1.5 毫克/千克),PD 的遗传毒性升高(p < 0.05)。组织病理学分析未显示 PD 在小鼠细胞和组织中的毒性。因此,我们的结果表明,PD 在小鼠和黑腹果蝇细胞中是一种有效的基因毒性免疫抑制剂。体细胞重组是 SMART 测试中观察到的诱导基因毒性的主要贡献者 (46%–82%)。

更新日期:2021-02-19
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