Protective effect of amifostine on busulfan induced DNA damage in human hepatoma cells

IF 2.8 4区医学 Q2 TOXICOLOGY

Toxicology Mechanisms and Methods Pub Date : 2017-01-02 DOI:10.1080/15376516.2016.1243601

Nasrin Ghassemi-Barghi, M. Etebari, A. Jafarian-dehkordi

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引用次数: 15

Abstract

Abstract Busulfan is one of the most effective chemotherapeutic agents used for the treatment of chronic myeloid leukemia. However, as a bifunctional alkylating agent, during clinical use several side effects may occur. In addition, several in vivo and in vitro studies of busulfan have shown a range of genotoxic effects including DNA strand break and inhibition of DNA synthesis. Amifostine, an organic thiophosphate compound, has been shown to exert an important cyto-protective effect in many tissues. The aim of this study was to explore whether amifostine protects against busulfan-induced genotoxicity in HepG2 cell line. Our results showed that amifostine reduced the genotoxic effects of busulfan significantly in both type of experiment conditions, as measured via comet assay. Furthermore, amifostine decreased the intracellular ROS generation induced by busulfan and also increased the intracellular GSH levels in HepG2 cells. Altogether, our results suggest a protective action of amifostine against busulfan cytotoxicity and genotoxicity via various pathways. The most protective effect was observed with amifostine when it was administrated 24 h before busulfan treatment.

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氨磷汀对丁硫凡诱导的人肝癌细胞DNA损伤的保护作用

布苏凡是治疗慢性髓系白血病最有效的化疗药物之一。然而，作为一种双功能烷基化剂，在临床使用过程中可能会出现一些副作用。此外，几项体内和体外研究已经显示出一系列的基因毒性作用，包括DNA链断裂和抑制DNA合成。氨磷汀是一种有机硫磷化合物，已被证明在许多组织中发挥重要的细胞保护作用。本研究的目的是探讨氨磷汀是否能保护HepG2细胞系免受布苏芬诱导的遗传毒性。我们的研究结果表明，在两种类型的实验条件下，氨磷汀都显著降低了布苏凡的遗传毒性作用，通过彗星试验进行了测量。此外，氨磷汀降低了丁硫凡诱导的细胞内ROS生成，并增加了HepG2细胞内GSH水平。总之，我们的研究结果表明氨磷汀通过多种途径对丁硫丹的细胞毒性和遗传毒性具有保护作用。在布硫凡治疗前24小时给予氨磷汀，其保护作用最大。

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来源期刊

Toxicology Mechanisms and Methods TOXICOLOGY-

自引率

3.10%

发文量

期刊介绍： Toxicology Mechanisms and Methods is a peer-reviewed journal whose aim is twofold. Firstly, the journal contains original research on subjects dealing with the mechanisms by which foreign chemicals cause toxic tissue injury. Chemical substances of interest include industrial compounds, environmental pollutants, hazardous wastes, drugs, pesticides, and chemical warfare agents. The scope of the journal spans from molecular and cellular mechanisms of action to the consideration of mechanistic evidence in establishing regulatory policy. Secondly, the journal addresses aspects of the development, validation, and application of new and existing laboratory methods, techniques, and equipment. A variety of research methods are discussed, including: In vivo studies with standard and alternative species In vitro studies and alternative methodologies Molecular, biochemical, and cellular techniques Pharmacokinetics and pharmacodynamics Mathematical modeling and computer programs Forensic analyses Risk assessment Data collection and analysis.