Tumor spectrum in the p53 heterozygous zeta globin-promoted Tg.AC (v-Ha-ras) bitransgenic mouse model.
Tumor spectrum in the p53 heterozygous zeta globin-promoted Tg.AC (v-Ha-ras) bitransgenic mouse model.
复制标题
p53 杂合 zeta 珠蛋白促进的 Tg.AC (v-Ha-ras) 双转基因小鼠模型中的肿瘤谱。
DOI：
10.1080/01926230490462129
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发表时间：
2004
影响因子：
1.5
通讯作者：
French,JohnE
中科院分区：
文献类型：
--
作者：
Martin,KeithR;Jokinen,MichaelP;Honeycutt,HaydenP;Quinn,Anita;Kari,FrankW;Barrett,JCarl;French,JohnE
使用双转基因小鼠癌症模型是研究特定致癌物的影响和组织特异性病变发生的有效方法。我们研究了一种新的p53杂合zeta珠蛋白促进的Tg.AC（v-Ha-ras）小鼠模型，因为这些小鼠含有致癌物诱导的ras癌基因和一个功能性p53肿瘤抑制等位基因，这两种基因在人类癌症中经常发生。我们的目的是在这种新的模型中表征短期对照和化学诱导的肿瘤谱。将小鼠置于含有20%大豆蛋白的基础半纯化饮食2周，然后随机分配至各组。随后，15只雄性和15只雌性小鼠经口灌胃给予单独的玉米油溶剂或含有苯并（a）芘（20 mg/kg体重）的玉米油溶剂，每周2次，持续10周，随后观察18周。小鼠表现出FVB/N、p53杂合子和Tg.AC小鼠模型的特征性病变。然而，观察到一系列独特的新病变，包括子宫平滑肌瘤，乳腺癌，乳腺鳞状细胞癌，腮腺唾液腺癌，这表明2种基因型的组织特异性相互作用。因此，这种双转基因模型可以提供进一步的洞察机制的相互作用的2个基因通常突变的肿瘤。
The use of a bitransgenic mouse model for cancer is an effective approach for studying the impact of specific carcinogens and the occurrence of tissue-specific lesions. We studied the novelp53heterozygous zeta globin-promoted Tg.AC (v-Ha-ras) mouse model because these mice contain a carcinogen-inducible ras oncogene and one functionalp53tumor suppressor allele, both of which occur frequently in human cancers. Our aim was to characterize the short-term control and chemically induced tumor spectrum in this novel model. Mice were placed on basal semipurified diet containing 20% soy protein for 2 weeks prior to random allocation to groups. Subsequently, 15 male and 15 female mice were administered corn oil vehicle alone or containing benzo(a)pyrene (20 mg/kg body weight) via oral gavage 2 times per week for 10 weeks with subsequent observation for 18 weeks. Mice exhibited lesions characteristic of FVB/N,p53heterozygous and Tg.AC mouse models. However, an array of unique, novel lesions were observed including uterine leiomyosarcomas, mammary gland carcinomas, mammary squamous cell carcinomas, and parotid salivary gland carcinomas suggesting tissue-specific interactions of the 2 genotypes. Thus, this bitransgenic model may provide further insight into the mechanistic interaction of 2 genes commonly mutated in neoplasia.