Analysis of accumulation of DNA double-strand breaks in mouse tissues by pulsed-field gel electrophoresis

IF 3.3 3区医学 Q2 PHARMACOLOGY & PHARMACY Toxicology and applied pharmacology Pub Date : 2025-02-20 DOI:10.1016/j.taap.2025.117278

Takeshi Terabayashi , Takako Sasaki , Toshimasa Ishizaki , Tadashi Tomo , Yoshihiro Nishida , Katsuhiro Hanada

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Abstract

Double-strand DNA breaks (DSBs) are among the most cytotoxic DNA lesions, which can lead to chromosomal instability and eventually cell death. The substances that can potentially induce DSB formation are thus regarded as genotoxic. To date, many genotoxicity tests for detecting DNA breaks have been designed. However, there are limited options available for measuring the accumulation of DSBs in vivo. In this study, we aimed to evaluate a method of detecting the DSBs formed by the direct action of genotoxic substances using pulsed-field gel electrophoresis (PFGE). This approach has the advantage of making it easier to distinguish between DSBs and single-strand DNA breaks (SSBs) induced by the direct action of genotoxic substances. To confirm the detection of DSBs using PFGE, we investigated their accumulation after treatment with cis-diamminedichloroplatinum(II) (cisplatin) or γ-rays in mouse organs. The results revealed the successful detection of cisplatin-induced DSB formation in mouse kidney and thymus and γ-ray-induced DSB formation in all organs. We also discuss the advantages of PFGE-based detection of DSBs in vivo.

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来源期刊

Toxicology and applied pharmacology 医学-毒理学

CiteScore

6.80

自引率

2.60%

发文量

309

审稿时长

32 days

期刊介绍： Toxicology and Applied Pharmacology publishes original scientific research of relevance to animals or humans pertaining to the action of chemicals, drugs, or chemically-defined natural products. Regular articles address mechanistic approaches to physiological, pharmacologic, biochemical, cellular, or molecular understanding of toxicologic/pathologic lesions and to methods used to describe these responses. Safety Science articles address outstanding state-of-the-art preclinical and human translational characterization of drug and chemical safety employing cutting-edge science. Highly significant Regulatory Safety Science articles will also be considered in this category. Papers concerned with alternatives to the use of experimental animals are encouraged. Short articles report on high impact studies of broad interest to readers of TAAP that would benefit from rapid publication. These articles should contain no more than a combined total of four figures and tables. Authors should include in their cover letter the justification for consideration of their manuscript as a short article.

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