Scientific Reports ( IF 3.8 ) Pub Date : 2023-01-31 , DOI: 10.1038/s41598-023-28825-4 Yuko Goto 1 , Arata Saito 1 , Kenji Takanobu 1 , Hideki Senoh 1 , Misae Saito 1 , Yumi Umeda 1 , Shotaro Yamano 1
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.
中文翻译:
使用 rasH2 小鼠模型进行的 26 周吸入研究中 2-溴丙烷的致癌性和睾丸毒性
2-溴丙烷(2-BP)在室温下是无色液体,用于工厂的封闭系统中,主要作为医药、农药和其他化学品的中间体。然而,2-BP的致癌性仍不清楚。 CByB6F1-Tg(HRAS)2Jic (rasH2) 转基因小鼠模型已被建立作为长期研究(1.5 年——一生)的替代方案,可在短短六个月内检测致癌性。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 小鼠暴露于 0、67、200 或 600 ppm 的 2-BP,每天 6 小时,每周 5 天,持续 26 周。收集所有组织和血液并进行生物学和组织病理学分析。结果显示,吸入 2-BP 的雄性和雌性 rasH2 小鼠的肺部肿瘤发展呈浓度依赖性增加,Peto 和 Poly-3 趋势测试显示这一点很显着。此外,在雄性 rasH2 小鼠中,发现 2-BP 是一种睾丸毒素。这项研究首次使用 rasH2 小鼠模型证明 2-BP 在雄性和雌性小鼠中具有致癌性,在雄性小鼠中具有睾丸毒素。