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首页> 外文期刊>Toxicology: An International Journal Concerned with the Effects of Chemicals on Living Systems >A toxicogenomic approach for identifying biomarkers for myelosuppressive anemia in rats.
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A toxicogenomic approach for identifying biomarkers for myelosuppressive anemia in rats.

机译：一种用于确定大鼠骨髓抑制性贫血生物标志物的毒物基因组学方法。

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摘要

Myelosuppressive anemia is a serious side effect associated with several drugs. Thus, there is an increasing demand for sensitive biomarkers for the early detection of myelosuppressive anemia during toxicological studies. We applied a toxicogenomic approach to identify useful biomarker genes reflecting myelosuppressive anemia in the rat liver. Expression of the hemoglobin beta chain complex (Hbb), aminolevulinic acid synthase 2 (Alas2), and cell division cycle 25 homolog B (Cdc25b) genes changed as a result of anemia induced by the myelosuppressive agents linezolid, cisplatin, and carboplatin, suggesting that these genes may be suitable biomarkers. Moreover, evaluation of perfused and unperfused livers indicated that changes in the expression of these genes originate in circulating reticulocytes in the liver. Erythroid differentiation-associated changes in expression of the Hbb, Alas2, and Cdc25b genes were confirmed in vitro using Friend leukemia cells. In conclusion, our current research provides novel evidence that gene expression in circulating reticulocytes contained in the liver changes dramatically under myelosuppressive conditions. While further large-scale validation studies are needed, our results indicate that the genes we identified might be useful biomarkers for the sensitive detection of myelosuppressive anemia in rats.
机译：骨髓抑制性贫血是与几种药物相关的严重副作用。因此，对于在毒理学研究中早期检测骨髓抑制性贫血的敏感生物标记物的需求不断增加。我们应用了毒理基因组学方法来鉴定可反映大鼠肝脏骨髓抑制性贫血的有用生物标志物基因。由于骨髓抑制剂利奈唑胺，顺铂和卡铂引起的贫血，血红蛋白β链复合物（Hbb），氨基乙酰丙酸合酶2（Alas2）和细胞分裂周期25同系物B（Cdc25b）基因的表达发生了变化，这表明这些基因可能是合适的生物标记。此外，对灌注和未灌注肝脏的评估表明，这些基因表达的变化起源于肝脏中循环的网织红细胞。在体外使用Friend白血病细胞证实了类红细胞分化相关的Hbb，Alas2和Cdc25b基因表达的变化。总之，我们目前的研究提供了新的证据，表明在骨髓抑制条件下，肝脏中循环网织红细胞中的基因表达发生了巨大变化。尽管需要进一步的大规模验证研究，但我们的结果表明，我们鉴定出的基因可能是敏感检测大鼠骨髓抑制性贫血的有用生物标志物。

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