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

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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.