关键词: 转基因小鼠, 癌前病变, 细胞周期, bax/bcl_2比值, 细胞增殖核抗原

Abstract: BACKGROUND AND AIM: To investigate the association of precancerous lesion development with cell cycle characteristics and expressive activities of genes such as bax, bcl_2 and PCNA and the relationship between these and p53mt expression in nasal and nasopharyngeal epithelia of TgN(p53mt_LMP1)/HT mice containing human mutant p53 (p53mt) gene and EB virus latent membrane protein 1 (LMP1). MATERIALS AND METHODS: The pathohistological changes in nasal and nasopharyngeal epithelial tissues in the fourth generation transgenic positive mice and negative mice aged 12 months were determined by H_E staining methods, cell cycle characteristics of nasal and nasopharyngeal epithelia were detected by flow cytometry, and expression activities of apoptosis_related genes such as p53mt, bax, bcl_2 and that of cell proliferation_related gene PCNA were assayed by immunohistochemistry in the same tissue samples. Then, a correlative analysis was carried out among the different sets of data to investigate the pathogenetic association of naturally developed precancerous lesion with the expression activities of apoptosis_ and cell proliferation_related genes in the target organs. RESULTS: The rates of precancerous lesion in nasal and nasopharyngeal epithelia of positively transgenic mice and negative ones were 63.64％ and 0 respectively, with very significant difference between them(P<0.01). Compared with that of negatively transgenic mice, the number of nasal or nasopharyngeal epithelial cells in G0/G1 phase was markedly decreased, and that in S and G2/M phases were obviously increased, with proliferation index (PI) enhanced significantly (P<0.01). The expression activities of p53mt, bcl_2 and PCNA were raised and that of bax was decreased significantly, with an increased ratio of bcl_2/bax (P<0.01). CONCLUSION: The expression of p53mt in TgN(p53mt_LMP1)/HT mice may cause the inhibition of bax expression at first,followed by the increased expression of bcl_2 and PCNA, with an elevated ratio of bcl_2/bax. Thereafter, the activity of apoptosis would be reduced and cellular proliferating potentiality strengthened,as measured by PI. As a result, precancerous lesion may occur in nasal and/or nasopharyngeal epithelium.

Key words: transgenic mouse, precancerous lesions, cell cycles, bax/bcl_2 ratio, PCNA