Enhancive effect of N,N'-dinitrosopiperazine on inducing precancerous lesion on nasal and/or nasopharyngeal epithelia of TgN(p53mt-LMP1)/HT mice  

作　　者：Dao-fa TIAN Ying-chun HE Fang-guo LU Fa-qing TANG 

机构地区：[1]Faculty of Integrative Medicine Changsha 410007, China) [2]Faculty cf Basic Medicine, Chinese Medicine University of Hunan, Changsha 410007, China [3]Department of Clinical Laboratory the First Xiangya Hospital, Central South University, Changsha 410008, China

出　　处：《Journal of Zhejiang University-Science B(Biomedicine & Biotechnology)》2009年第3期172-179,共8页浙江大学学报（英文版）B辑（生物医学与生物技术）

基　　金：supported by the National Natural Science Foundation of China (Nos. 30672738, 30572455 and 30572408);Hunan Provincial Natural Science Foundation for Distinguished Young Scholars (No. 03JJY1006);for General Projects (Nos. 05JJ40029 and 07JJ6038);the Research Foundation of Hunan Provincial Scientific and Technological Department for International Cooperative Academic Projects (No. 06WK3016);the Research Foundation of Hunan Provincial Education Department for Outstanding Young Scholars (No. 06B070), China

摘　　要：Objective： To investigate the enhancive effect ofN, N′-dinitrosopiperazine （DNP） on induced carcinogenesis in nasal and/or nasopharyngeal epithelia among TgN（p53mt-LMP1）/HT transgenic mice to examine the underlying mechanism for the development of nasopharyngeal carcinoma （NPC）. Methods： TgN（p53mt-LMP1）/HT transgenic mice and the same strain of C57BL/6J wild-type mice both at the age of 5 months were randomly divided into 2 groups in parallel, respectively, i.e., TgN（p53mt-LMP1）/HT cancerous lesion-inducing group （T1）, TgN（p53mt-LMP1）/HT control group （TC）, C57BL/6J cancerous lesion-inducing group （CI）, and C57BL/6J control group （CC）. TI and CI mice were treated only with DNP for 16 weeks, twice each week, while TC and CC mice were given the same volume of saline as controls.At the end of treatment, animals were sacrificed to collect epithelial tissue samples from nasal cavity and nasopharynx for pathohistological evaluation by hacmatoxylin and eosin （HE） staining and for determination on the expression ofTRAF2, c-Jun, and p 16 by immunohistochemistry. Results： Atypical hyperplasia was more significant in the samples of TI than in those of TC, CI, and CC, with the rates of lesions being 90%, 10%, 0, and 0 （P〈0.01） respectively, though DNP was used alone in a much shortened inducing period at less dosage and without the use of carcinogenic promoter 12-0-tetradecanoylphorbol-13-acetate as usual. The expressions of tumor necrosis factor （TNF） receptor-associated factor 2 （TRAF2） and c-Jun in these samples were significantly up-regulated in TI （P〈0.0 I）, while tbe expression of p16 was significantly lower in TI than in the other groups （P〈0.01）. Conclusion： TgN（p53mt-LMPI）/HT mice hold inherited constitutional defect in immune surveillance function, which can be aggravated by environmental carcinogens, such as DNP used even though in a much less strength. The enhanced carcinogenesis-inducing effect of DNP on TgN（p53mt-LMP1）/HT miObjective:To investigate the enhancive effect of N,N'-dinitrosopiperazine(DNP) on induced carcinogenesis in nasal and/or nasopharyngeal epithelia among TgN(p53mt-LMP1)/HT transgenic mice to examine the underlying mechanism for the development of nasopharyngeal carcinoma(NPC). Methods:TgN(p53mt-LMP1)/HT transgenic mice and the same strain of C57BL/6J wild-type mice both at the age of 5 months were randomly divided into 2 groups in parallel,respectively,i.e.,TgN(p53mt-LMP1)/HT cancerous lesion-inducing group(TI),TgN(p53mt-LMP1)/HT control group(TC),C57BL/6J cancerous lesion-inducing group(CI),and C57BL/6J control group(CC). TI and CI mice were treated only with DNP for 16 weeks,twice each week,while TC and CC mice were given the same volume of saline as controls. At the end of treatment,animals were sacrificed to collect epithelial tissue samples from nasal cavity and nasopharynx for pathohistological evaluation by haematoxylin and eosin(HE) staining and for determination on the expression of TRAF2,c-Jun,and p16 by immunohistochemistry. Results:Atypical hyperplasia was more significant in the samples of TI than in those of TC,CI,and CC,with the rates of lesions being 90%,10%,0,and 0(P<0.01) respectively,though DNP was used alone in a much shortened inducing period at less dosage and without the use of carcinogenic promoter 12-O-tetradecanoylphorbol-13-acetate as usual. The expressions of tumor necrosis factor(TNF) recep-tor-associated factor 2(TRAF2) and c-Jun in these samples were significantly up-regulated in TI(P<0.01),while the expression of p16 was significantly lower in TI than in the other groups(P<0.01). Conclusion:TgN(p53mt-LMP1)/HT mice hold inherited con-stitutional defect in immune surveillance function,which can be aggravated by environmental carcinogens,such as DNP used even though in a much less strength. The enhanced carcinogenesis-inducing effect of DNP on TgN(p53mt-LMP1)/HT mice should be closely associated with abnormal signaling of activator protein-1(AP-1) pathway,especially up-regulated expres

关 键 词：Nasal epithelia Nasopharyngeal epithelia Precancerous lesions N N′-dinitrosopiperazine （DNP） Activator protein-1（AP- 1） pathway Signal transduction 

分 类 号：Q78[生物学—分子生物学] S852.65[农业科学—基础兽医学]