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

用4-硝基喹啉1-氧化物（4 NQO）处理两种大鼠（DA和WF），研究了舌癌发生过程中p53蛋白的免疫组化表达。设计动物实验以观察两种不同方式的两种菌株之间的致癌性差异，即4 NQO治疗持续至濒死状态或使用确定的治疗方案。免疫组化结果显示，在已建立的SCC中，DA和WF大鼠的p53蛋白阳性率相似，但在发育不良的舌上皮中，DA大鼠的p53阳性细胞团多于WF大鼠，且多呈随机分布，DA大鼠的p53反应早于WF大鼠，DA大鼠p53阳性细胞团在实验后期明显增多，而WF大鼠p53阳性细胞团数目无明显变化。7只DA和2只WF大鼠舌组织DNA中p53基因突变阳性率为13.4%。在所有9只大鼠中均观察到一种非常常见的基因突变，即外显子5的TGC _3 TAC转换（密码子174）。总之，64.3%的舌中p53蛋白免疫组化阳性的大鼠表现出一些p53基因突变。其余35.7%（5只DA大鼠）在其舌粘膜中有p53蛋白阳性簇，然而，它们未显示任何可检测的p53基因突变。因此，本研究结果可能表明，在大鼠舌癌发生的早期阶段，尽管没有p53基因突变，p53蛋白异常发挥了重要作用。这些结果还表明，在DA和WF大鼠之间，p53对4 NQO的反应可能存在品系差异，这些差异可能有助于形成对比的致癌性肥胖。

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.