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Received: 2008-06-08

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Journal of Zhejiang University SCIENCE B 2009 Vol.10 No.3 P.172~179

10.1631/jzus.B0820186


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


Author(s):  Dao-fa TIAN, Ying-chun HE, Fang-guo LU, Fa-qing TANG

Affiliation(s):  Faculty of Integrative Medicine; more

Corresponding email(s):   yingchunhe@yahoo.com.cn

Key Words:  Nasal epithelia, Nasopharyngeal epithelia, Precancerous lesions, N, N'-dinitrosopiperazine (DNP), Activator protein-1 (AP-1) pathway, Signal transduction


Dao-fa TIAN, Ying-chun HE, Fang-guo LU, Fa-qing TANG. Enhancive effect of N,N'-dinitrosopiperazine on inducing precancerous lesion on nasal and/or nasopharyngeal epithelia of TgN(p53mt-LMP1)/HT mice[J]. Journal of Zhejiang University Science B, 2009, 10(3): 172~179.

@article{title="Enhancive effect of N,N'-dinitrosopiperazine on inducing precancerous lesion on nasal and/or nasopharyngeal epithelia of TgN(p53mt-LMP1)/HT mice",
author="Dao-fa TIAN, Ying-chun HE, Fang-guo LU, Fa-qing TANG",
journal="Journal of Zhejiang University Science B",
volume="10",
number="3",
pages="172~179",
year="2009",
publisher="Zhejiang University Press & Springer",
doi="10.1631/jzus.B0820186"
}

%0 Journal Article
%T Enhancive effect of N,N'-dinitrosopiperazine on inducing precancerous lesion on nasal and/or nasopharyngeal epithelia of TgN(p53mt-LMP1)/HT mice
%A Dao-fa TIAN
%A Ying-chun HE
%A Fang-guo LU
%A Fa-qing TANG
%J Journal of Zhejiang University SCIENCE B
%V 10
%N 3
%P 172~179
%@ 1673-1581
%D 2009
%I Zhejiang University Press & Springer
%DOI 10.1631/jzus.B0820186

TY - JOUR
T1 - Enhancive effect of N,N'-dinitrosopiperazine on inducing precancerous lesion on nasal and/or nasopharyngeal epithelia of TgN(p53mt-LMP1)/HT mice
A1 - Dao-fa TIAN
A1 - Ying-chun HE
A1 - Fang-guo LU
A1 - Fa-qing TANG
J0 - Journal of Zhejiang University Science B
VL - 10
IS - 3
SP - 172
EP - 179
%@ 1673-1581
Y1 - 2009
PB - Zhejiang University Press & Springer
ER -
DOI - 10.1631/jzus.B0820186


Abstract: 
Objective: 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) receptor-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 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 mice should be closely associated with abnormal signaling of activator protein-1 (AP-1) pathway, especially up-regulated expressions of TRAF2 and c-Jun, and down-regulated expression of p16.

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