Oral Cavity Carcinogenesis Modeled in Carcinogen-Treated Mice

Abstract

In the present study, oral squamous cell carcinoma (OSCC) was induced in a mouse model with 20 μg/ml 4-Nitroquinoline-1-oxide (4NQO) solution in drinking water. 120 six-week-old male Balb/C mice were randomly divided into an experimental group (n=110) and a control group (n=10). They were sacrificed after 16 to 48 weeks of exposure to allow for histopathological and immuhistochemical examinations. Gross changes could be observed, including white changes, leukoplakia, erythroplakia, ulceration and papillary tumor appearance on the mucosa of the tongue dorsum of the experimental group mice during the carcinogenesis period. At the same time, no visible and histopathological changes in tongue epithelium were observed in the control group. Survivin expression was positive in dysplasia and OSCC groups but not in normal mucosa, and correlated positively with PCNA expression. Also, survivin protein staining showed statistical significance in the dysplasia group (p<0.05) but not in the OSCC group (p<0.05). Furthermore, PCNA Labelling Index (PI) in survivin positive specimens were found significantly higher than it in survivin negative specimens (p<0.01). These results showed that survivin might be closely related to cell proliferation, differentiation and carcinogenesis. It also showed that survivin might promote unrestricted multiplication and dedifferentiation of cells, making the tumor taking a malignant behavior through promoting cell mitosis, cell apoptosis, and enhancing cell proliferative activity. Therefore, the detection of expression of survivin and PCNA is helpful for early diagnosis of OSCC.