Co-treating with arecoline and 4-nitroquinoline 1-oxide to establish a mouse model mimicking oral tumorigenesis.
The aim of this study was to establish an effective mouse model of oral cancer and to use this model to identify potential markers of oral tumor progression. C57BL/6JNarl mice were treated with arecoline, 4-nitroquinoline 1-oxide (4-NQO), or both arecoline and 4-NQO in high and low doses for 8 weeks to induce oral tumor. The induced oral lesions were observed for 20 weeks to assess the efficiency of cancer induction and survival rate of the mice. In addition, two target proteins that are frequently overexpressed during tongue cancer tumorigenesis, alphaB-crystallin and Hsp27, were examined by immunohistochemical analysis. In mice exposed to 4-NQO (200 microg/mL) and arecoline (500 microg/mL), the tongue lesions showed evidence of hyperplasia, papilloma, dysplasia, and carcinoma, and the lesions were pathologically similar to those lesions in human oral cancer. The tongue tumor incidence rate was 100% in mice exposed to concomitant 4-NQO (200 microg/mL) and arecoline (500 microg/mL) treatment, 57% in mice exposed to 4-NQO only, and 0% in mice exposed to arecoline only. Immunohistochemical analysis demonstrated that, consistent with human studies, alphaB-crystallin and Hsp27 were upregulated in murine oral tumors. In conclusion, we have established a powerful animal model that enables the study of the promoting effects of arecoline on tongue tumorigenesis. Data subsequently attained from this mouse model support a role for alphaB-crystallin and Hsp27 as clinical markers for tumor progression.
Department of Biochemistry, College of Medicine, China Medical University, 91 Hsueh-Shih Road, Taichung 40402, Taiwan, ROC. nwchang@mail.cmu.edu.tw
Nai-Wen
NW
Chang
Ren-Jeng
RJ
Pei
Hsien-Chang
HC
Tseng
Kun-Tu
KT
Yeh
Hsu-Chin
HC
Chan
Miau-Rong
MR
Lee
Chingju
C
Lin
Wen-Tsong
WT
Hsieh
Ming-Ching
MC
Kao
Ming-Hsui
MH
Tsai
Chin-Fen
CF
Lin
D015112:4-Nitroquinoline-1-oxide / Q000633:toxicity*; D000818:Animals; D001115:Arecoline / Q000633:toxicity*; D002273:Carcinogens / Q000633:toxicity*; D004195:Disease Models, Animal; D018450:Disease Progression; D055551:HSP27 Heat-Shock Proteins / Q000378:metabolism; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D016019:Survival Analysis; D014062:Tongue Neoplasms / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D015854:Up-Regulation; D038203:alpha-Crystallin B Chain / Q000378:metabolism
D002273:Carcinogens; C525420:Cryab protein, mouse; D055551:HSP27 Heat-Shock Proteins; D038203:alpha-Crystallin B Chain; D001115:Arecoline; D015112:4-Nitroquinoline-1-oxide