Heterozygous p53-deficient mice are not susceptible to 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) carcinogenicity.
Heterozygous p53-deficient mice are not susceptible to 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) carcinogenicity.
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杂合 p53 缺陷小鼠对 2-氨基-3,8-二甲基咪唑[4,5-f]喹喔啉 (MeIQx) 致癌性不敏感。
DOI：
10.1016/s0304-3835(99)00036-1
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发表时间：
1999
期刊：
影响因子：
9.7
通讯作者：
H. Tsuda
中科院分区：
文献类型：
--
作者：
C. B. Park;D. J. Kim;N. Uehara;N. Takasuka;B. T. Hiroyasu;H. Tsuda
2-氨基-3，8-二甲基咪唑并[4，5-f]喹喔啉（MeIQx）是一种非常强的诱变剂，可诱发CDF 1小鼠的肝、肺和造血系统肿瘤以及F344大鼠的肝、Zymbal腺和皮肤肿瘤。转基因敲除小鼠的最新发展允许它们的引入用于由于肿瘤的快速发展而对环境致癌物的敏感筛选。发现P53基因缺陷小鼠（p53−/−）自发发生恶性淋巴瘤和血管肉瘤，而杂合子（p53+/−）小鼠在用N-丁基-N-（4-羟丁基）亚硝胺治疗时显示膀胱肿瘤的高发病率。在本研究中，为了确定p53基因敲除小鼠是否可用于筛选杂环胺（HCA）的短期测定模型，检查了作为代表性化合物的MeIQx在低剂量下的作用。雄性和雌性p53+/−小鼠和野生型同窝仔（p53+/+）连续给予含0、0.1、1、10和100 ppm MeIQx的饲料1年。除接受10 ppm MeIQx处理的雄性动物肝腺瘤增加外，未观察到肿瘤诱导的显著差异。结果表明，p53+/−小鼠用于HCA的短期致癌性试验没有实际优势。
2-Amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) is a very potent mutagen which induces tumors in the liver, lung and hematopoietic system of CDF1mice and the liver, Zymbal gland and skin in F344 rats. The recent development of transgenic knockout mice allows their introduction for sensitive screening of environmental carcinogens due to the rapid development of tumors. P53 gene deficient mice (p53−/−) were found to spontaneously develop malignant lymphoma and hemangiosarcoma, whereas heterozygotes (p53+/−) mice display a high incidence of tumors of the urinary bladder when treated with N-butyl-N-(4-hydroxybutyl)nitrosamine. In the present study, to determine whether p53 gene knockout mice can be utilized in a short-term assay model for the screening of heterocyclic amines (HCAs), the effects of MeIQx, as a representative compound, at low doses were examined. Male and female p53+/− mice and wild type littermates (p53+/+) were continuously given diets containing 0, 0.1, 1, 10 and 100 ppm MeIQx for 1 year. No significant difference in tumor induction was observed other than an increase in liver adenomas in males receiving 10 ppm MeIQx treatment. The results indicate that p53+/− mice have no practical advantages for use in short-term carcinogenicity tests of HCAs.
影响因子：
8
作者：
Burns Pa;Christopher J. Kemp;Gannon Jv;David P. Lane;R. Bremner;Allan Balmain
通讯作者：
Burns Pa;Christopher J. Kemp;Gannon Jv;David P. Lane;R. Bremner;Allan Balmain