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用于六个月致癌性研究的携带人类原型c-Ha-ras基因的转基因小鼠自发和诱发肿瘤的病理特征。

Pathological features of spontaneous and induced tumors in transgenic mice carrying a human prototype c-Ha-ras gene used for six-month carcinogenicity studies.

作者信息

Mitsumori K, Koizumi H, Nomura T, Yamamoto S

机构信息

Division of Pathology, National Institute of Health Sciences, Tokyo, Japan.

出版信息

Toxicol Pathol. 1998 Jul-Aug;26(4):520-31. doi: 10.1177/019262339802600408.

Abstract

To validate the transgenic (Tg) mouse carrying a human prototype c-Ha-ras gene (rasH2 mouse) as a model for short or medium-term carcinogenicity testing, 6-mo carcinogenicity studies using more than 30 chemicals, including carcinogens and noncarcinogens, have been performed. The results obtained so far indicate that rasH2 mice are generally much more susceptible to both mutagenic and nonmutagenic carcinogens than are non-Tg mice, pointing to advantageous application for detection of carcinogenic potential. In this review, histopathological features and diagnostic criteria for spontaneous and induced-tumors observed in our 6-mo carcinogenicity studies are described. Incidences of spontaneous tumors were generally low in rasH2 mice during the 6-mo studies, although values for lung adenomas and splenic hemangiosarcomas were higher than those in the control non-Tg mice. A few forestomach papillomas and skin papillomas were also observed in the control rasH2 mice. The target organs in rasH2 mice treated with known carcinogens were not always identical to those in the treated B6C3F1 mice in 2-yr carcinogenicity bioassays, with forestomach squamous cell tumors, lung alveolar epithelial tumors and/or hemangiosarcomas in the spleen observed in addition to some but not all of the lesions in target organs observed in non-Tg mice in long-term carcinogenicity bioassays. The results of the present histological study suggest that the lung, spleen and/or forestomach, where tumors are induced in rasH2 mice treated with known carcinogens, should be regarded as informative target organs in addition to the target organs reported in previous long-term carcinogenicity bioassays in rats and mice.

摘要

为验证携带人类原型c-Ha-ras基因的转基因(Tg)小鼠(rasH2小鼠)作为短期或中期致癌性测试模型的有效性,已使用30多种化学物质(包括致癌物和非致癌物)进行了为期6个月的致癌性研究。目前获得的结果表明,与非Tg小鼠相比,rasH2小鼠通常对诱变和非诱变致癌物都更敏感,这表明其在检测致癌潜力方面具有优势。在本综述中,描述了在我们为期6个月的致癌性研究中观察到的自发肿瘤和诱导肿瘤的组织病理学特征及诊断标准。在为期6个月的研究中,rasH2小鼠的自发肿瘤发生率总体较低,尽管肺腺瘤和脾血管肉瘤的值高于对照非Tg小鼠。在对照rasH2小鼠中也观察到少数前胃乳头瘤和皮肤乳头瘤。用已知致癌物处理的rasH2小鼠的靶器官并不总是与在两年致癌性生物测定中处理的B6C3F1小鼠的靶器官相同,除了在长期致癌性生物测定中在非Tg小鼠中观察到的靶器官中的一些(但不是全部)病变外,还观察到前胃鳞状细胞瘤、肺泡上皮肿瘤和/或脾血管肉瘤。本组织学研究结果表明,在用已知致癌物处理的rasH2小鼠中诱导肿瘤的肺、脾和/或前胃,除了先前在大鼠和小鼠长期致癌性生物测定中报告的靶器官外,应被视为信息丰富的靶器官。

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