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泼尼松在小鼠和黑腹果蝇中具有遗传毒性。

Prednisone is genotoxic in mice and Drosophila melanogaster.

机构信息

Laboratory of Radiobiology and Mutagenesis, Department of Genetics, Institute of Biological Sciences, Campus Samambaia, Universidade Federal de Goiás, 74690-900, Goiânia, GO, Brazil.

Laboratory of Radiobiology and Mutagenesis, Department of Histology, Embryology and Cell Biology, Institute of Biological Sciences, Campus Samambaia, Universidade Federal de Goiás, 74690-900, Goiânia, GO, Brazil.

出版信息

Mutat Res Genet Toxicol Environ Mutagen. 2021 May;865:503334. doi: 10.1016/j.mrgentox.2021.503334. Epub 2021 Feb 14.

Abstract

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.

摘要

泼尼松龙(PD)是治疗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肿瘤形成增加有关。由于遗传毒性与癌症发展风险增加有关,因此本研究使用 SMART/wing 测定法在黑腹果蝇和微核试验和彗星试验在小鼠骨髓细胞中评估了 PD 的遗传毒性和细胞毒性活性。此外,还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 测定中,与阴性对照相比(p < 0.05),PD 在所有测试浓度(0.375、0.75、1.5 和 2.0 mg/mL)下均显示出显著的遗传毒性活性。微核试验和彗星试验也显示 PD 在所有治疗条件下(24、48 和 120 h,剂量范围为 0.5 至 1.5 mg/kg)均具有升高的遗传毒性(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 是小鼠和 D. melanogaster 细胞中一种有效的遗传毒性免疫抑制剂。体细胞重组是 SMART 试验中观察到的诱导遗传毒性的主要贡献者(46%-82%)。

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Prednisone is genotoxic in mice and Drosophila melanogaster.泼尼松在小鼠和黑腹果蝇中具有遗传毒性。
Mutat Res Genet Toxicol Environ Mutagen. 2021 May;865:503334. doi: 10.1016/j.mrgentox.2021.503334. Epub 2021 Feb 14.
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