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使用 rasH2 小鼠模型进行的为期 26 周的吸入研究中 2-溴丙烷的致癌性和睾丸毒性。

Carcinogenicity and testicular toxicity of 2-bromopropane in a 26-week inhalation study using the rasH2 mouse model.

机构信息

Japan Bioassay Research Center, Japan Organization of Occupational Health and Safety, 2445 Hirasawa, Hadano, Kanagawa, 257-0015, Japan.

出版信息

Sci Rep. 2023 Jan 31;13(1):1782. doi: 10.1038/s41598-023-28825-4.

Abstract

2-Bromopropane (2-BP) is a colorless liquid at room temperature and is used in closed systems in factories, mainly as an intermediate for medicines, pesticides, and other chemicals. However, the carcinogenicity of 2-BP is still unknown. The CByB6F1-Tg(HRAS)2Jic (rasH2) transgenic mouse model has been established as an alternative to long-term studies (1.5 years-lifetime) to detect carcinogenicity in as short a time as six months. We performed a 26-week inhalation exposure study of 2-BP using the rasH2 mouse model. Male and female rasH2 mice were exposed to 0, 67, 200, or 600 ppm of 2-BP for 6 h/day, 5 days/week for 26 weeks. All tissues and blood were collected and subjected to biological and histopathological analyses. The results showed a concentration-dependent increase in lung tumor development in male and female rasH2 mice exposed by inhalation to 2-BP, which was significant by Peto's and Poly-3 trend tests. Furthermore, in male rasH2 mice, 2-BP was found to be a testicular toxin. This study is the first to demonstrate that 2-BP is carcinogenic in male and female mice and a testicular toxin in male mice using the rasH2 mouse model.

摘要

2-溴丙烷(2-BP)在室温下为无色液体,在工厂的封闭系统中用作药物、农药和其他化学品的中间体。然而,2-BP 的致癌性尚不清楚。CByB6F1-Tg(HRAS)2Jic (rasH2)转基因小鼠模型已被建立为替代长期研究(1.5 年寿命)的方法,以在尽可能短的时间内(6 个月)检测致癌性。我们使用 rasH2 小鼠模型进行了为期 26 周的 2-BP 吸入暴露研究。雄性和雌性 rasH2 小鼠分别暴露于 0、67、200 或 600 ppm 的 2-BP 中,每天 6 小时,每周 5 天,共 26 周。收集所有组织和血液进行生物和组织病理学分析。结果表明,雄性和雌性 rasH2 小鼠经吸入暴露于 2-BP 后,肺部肿瘤的发展呈浓度依赖性增加,Peto 和 Poly-3 趋势检验均有统计学意义。此外,在雄性 rasH2 小鼠中,发现 2-BP 是一种睾丸毒素。本研究首次证明,使用 rasH2 小鼠模型,2-BP 对雄性和雌性小鼠具有致癌性,对雄性小鼠具有睾丸毒素作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f8f7/9889353/d53a2c54232f/41598_2023_28825_Fig1_HTML.jpg

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