GST-p and p53 in 4NQO-induced tongue carcinomas of two strains of rats

4NQO 诱导的两种大鼠舌癌中的 GST-p 和 p53

基本信息

批准号：
09470414
负责人：
KITANO Motoo
金额：
$ 3.07万
依托单位：
Kagoshima University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
1997
资助国家：
日本
起止时间：
1997 至 1998
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-09470414/
关键词：
4NQO tongue carcinoma DA rat WF rat Susceptible gene Resistant gene p53 GST-p GSTーp ラット舌癌 GST-P P53 系統差

项目摘要

Immunohistochemical expression of p53 protein during rat lingual carcinogenesis was studied using two strains of rats [Dark-Agouti (DA) and Wistar/Furth (WF) rats] treated with 4-nitroquinoline 1-oxide (4NQO). Animal experiments were designed to look into differences in carcinogenesity between the two strains in two different fashions, i.e. 4NQO treatment being lasted until the moribund state or using a defined treatment schedule. Although the immunohistochemical results showed that the positive ratio of p53 protein in the established SCCs was similar between DA and WF rats, the clusters of p53 positive cells, usually situated in radom groups in the dysplastic lingual epithelium, were greater in numbers in DA rats than in WF.Reactivity of p53 in DA rats was detected earlier than that in WF, and marked increase of p53 positive clusters in DA rats was noted at the later stages of the experiment, whereas in WF rats the number of p53 positive clusters seemed to be unchanged. It was also demonstrated that DNA samples of the tongue tissues of 7 DA and 2 WF rats (13.4%) showed positive mutations in p53 gene. A very common gene mutation was observed in exon 5 (TGC _3 TAC transitions at codon 174) in all 9 rats. In summary, 64.3 % of the rats with immunohistochemically positive p53 protein in the tongue exhibited some p53 gene mutations. The remaining 35.7 % (5 DA rats) had p53 protein positive clusters in their lingual mucosae, however, they did not show any detectable p53 gene mutations. Thus, the present results may suggest p53 protein abnormalities play some important roles at the earlier stages of rat lingual carcinogenesis inspite of the absence of p53 gene mutations. These results also suggest that there may be strain differences in the p53 response to 4NQO between DA and WF rats, and these differences may contribute to the contrasting carcinogenesity.

使用用 4-硝基喹啉 1-氧化物 (4NQO) 处理的两种大鼠品系 [Dark-Agouti (DA) 和 Wistar/Furth (WF) 大鼠] 研究了大鼠舌癌发生过程中 p53 蛋白的免疫组织化学表达。动物实验旨在以两种不同的方式研究两种菌株之间致癌性的差异，即持续 4NQO 治疗直至垂死状态或使用明确的治疗方案。尽管免疫组化结果显示，DA和WF大鼠所建立的SCC中p53蛋白的阳性率相似，但DA大鼠中p53阳性细胞簇的数量多于DA大鼠，这些细胞簇通常位于发育不良的舌上皮中的随机群中。 DA 大鼠中 p53 的反应性比 WF 更早检测到，并且在实验后期注意到 DA 大鼠中 p53 阳性簇显着增加，而在 WF 大鼠中，p53 阳性簇的数量似乎没有变化。还发现7只DA大鼠和2只WF大鼠（13.4%）的舌组织DNA样本显示p53基因阳性突变。在所有 9 只大鼠的外显子 5（密码子 174 处的 TGC _3 TAC 转换）中观察到非常常见的基因突变。综上所述，舌内p53蛋白免疫组化阳性的大鼠中有64.3%表现出某些p53基因突变。其余 35.7%（5 只 DA 大鼠）的舌粘膜中存在 p53 蛋白阳性簇，但是，它们没有表现出任何可检测到的 p53 基因突变。因此，目前的结果可能表明，尽管不存在p53基因突变，p53蛋白异常在大鼠舌癌发生的早期阶段发挥着一些重要作用。这些结果还表明，DA 和 WF 大鼠之间 p53 对 4NQO 的反应可能存在菌株差异，这些差异可能导致对比的致癌性。