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

• 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

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4-硝基喹啉1-氧化物（4NQO）治疗的两种大鼠[dark-agouti（da）和Wistar/furth（WF）大鼠（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。设计动物实验以研究两种不同时尚中两种菌株之间的致癌性差异，即4NQO治疗持续到垂直状态或使用定义的治疗时间表。尽管免疫组织化学结果表明，在既定的SCC中p53蛋白在DA和WF大鼠之间的阳性比率相似，但p53阳性细胞的簇通常位于p53阳性细胞的簇中，在发育不良的语言上皮中的radom基团中，DA大鼠的数量比WF的p53在da大鼠中的数量更大，而在da ff的p53中，p53的p53在da cluse and pl and da ff。在实验的后期，在DA大鼠中发现了大鼠，而在WF大鼠中，p53阳性簇的数量似乎没有变化。还证明7 DA和2 WF大鼠的舌组织的DNA样品（13.4％）在p53基因中显示阳性突变。在所有9只大鼠中，在外显子5中观察到非常常见的基因突变（TGC _3 TAC TAC转变）。总之，舌中有64.3％的大鼠具有免疫组织化学上阳性p53蛋白的大鼠表现出一些p53基因突变。其余35.7％（5 DA大鼠）在其舌粘膜中具有p53蛋白阳性簇，但是，它们没有显示出任何可检测到的p53基因突变。因此，目前的结果可能表明p53蛋白异常在大鼠舌癌变的早期阶段起着一些重要作用，尽管没有p53基因突变。这些结果还表明，p53对DA和WF大鼠之间对4NQO的反应可能存在菌株差异，这些差异可能有助于对比癌性。

项目成果

T-J Li,M Kitano: "Oriental Kimura's disease and its relation to angiolymphoid hyperplasia with eosinophilia(ALHE)." South Pacific Study. 17. 287-300 (1997)

T-J Li，M Kitano：“东方木村氏病及其与血管淋巴样增生伴嗜酸性粒细胞增多 (ALHE) 的关系。”

K Kubo,N Tsukasa,M Uehara,Y Izumi,M Orino,M Kitano,T Sueda: "Calcium and silicon from bioactive glass concerned with formation of nodules in periodontal-ligament fibroblasts in vitro." J Oral Rehabilit. 24. 70-75 (1997)

K Kubo、N Tsukasa、M Uehara、Y Izumi、M Orino、M Kitano、T Sueda：“生物活性玻璃中的钙和硅与体外牙周膜成纤维细胞结节的形成有关。”

T Takasaki,S Akiba,Y Sagara,H Yoshida: "Histological and biolobical characteristics of microinvasion in mammary carcinomas < 2cm in diameter." Pathol Intern. 48. 800-80 (1998)

T Takasaki、S Akiba、Y Sagara、H Yoshida：“直径 < 2 厘米的乳腺癌微侵袭的组织学和生物学特征。”

K Takahashi,G H Nuckolls,O Tanaka,I Semba,I Takahashi,R Dashner,L Shum,H C Slavikin: "Adenovirus-mediated ectopic expression of Msx2 in even-numbered thombomeres induces apoptotic elimination of cranial neural crest cells in ovo." Development. 125. 1627-1

K Takahashi,G H Nuckolls,O Tanaka,I Semba,I Takahashi,R Dashner,L Shum,H C Slavikin：“腺病毒介导的偶数 thombomeres 中 Msx2 的异位表达诱导卵内颅神经嵴细胞的凋亡消除。”

T-J Li, M Kitano: "Reviewing the unicystic ameloblastocma : a clinicopathologically distinct entity" Oral Med Pathol. 2. 61-68 (1997)

T-J Li，M Kitano：“回顾单囊性成釉细胞瘤：一种临床病理学上不同的实体”口腔医学病理学。