The Application Of Golden Hamster Buckle Pouch Carcinogenesis Model In Heavy Ion Irradiation

Objective:To establish hamsters buckle pouch carcinogenesis model by DMBA injection method, The tumor process changes were observed dynamically. To study the effects of trace elements and the expression of apoptosis related genes Survivin, Caspase-3 in hamster buckle pouch carcinogenesis model after carbon ion beams irradiation, so as to provide experimental evidence for Heavy Ion Clinical Therapy of Oral Cancer and risk assessment for Space Radiation.Materials and Methods:1.This study selected 81 healthy hamsters, they were randomly divided into 3 groups, including the control group (6), the painted group (15), the injected group (60) (also points A, B, C, D, E 5 Groups).With the DMBA acetone solution injection group, The concentration were used to set up for 0.5%,0.4%,0.3%,0.2%,and 0.1%.but the concentration in the painted group was fit for 0.5%. to induce buckle pouch carcinogenesis model in Syrian Golden Hamsters. For the general observation of the model, the body weight has been monitored and the tumor growth rate calculated. Using histological analysis of the similarities and differences in two methods with different pathological stages of.the carcinogenesis process The concentration of injection method by the screening to establish the appropriate carcinogenesis model of oral squamous cell carcinoma.2. Exposed with carbon ion beam irradiation of cheek pouch carcinoma in hamster, Observation 0,4,6,8,12 Gy dosage of heavy ion beams on the bearing hamster cheek pouch carcinoma of trace elements of content in blood. Application of flame atomic absorption spectroscopy determinated to flexion-extension (Fe) radiographs, copper (Cu), zinc (Zn) and magnesium (Mg), calcium (Ca) the content of trace elements in serum.3. Immunohistochemical SP method was detected the expression of Survivin and Caspase-3 protein of cheek pouch carcinogenesis in 40 cases bearing golden hamster and to explore on the impact of tumor tissue in Carbon ion beams irradiation.Results:1 The injection concentrations (0.4%,0.3%,0.2%,0.1%) of DMBA acetone solution have induced the tumors. Respectively, at 13W,9W,12W,16W, the average size is about 0.8cm× 0.6cm×0.5cm; the carcinogenesis rates at 12W were respectively 25%,87%,42%,58%; but 0.5% DMBA solution with painted group, the carcinogenesis rate was 48%,the death rate was 37%. Well differentiated cheek squamous cell carcinoma was obtained at 18W.2 In the hamsters borne tumor, the contents of Fe, Zn, Cu and Mg in experimental groups with cheek pouch carcinoma were significantly lower than normal group(P<0.05). After irradiated by 0, 4,6,8,12Gy heavy ion beams, the 4Gy group showed a tendency downward. When the irradiation dose reached 6Gy, the contents of Fe, Zn increased. When it reached 12Gy, the contents decreased.. While Cu, Ca and Mg contents in the group at 8Gy reached to their highest value, and had become lowering until 12Gy. All of the results showed a dose-reaction relationship (P<0.05).3 The number of the expression of positive Survivin protein were 28 among 40 cases in oral squamous cell carcinoma, the positive rate was 70%, but there was no positive individual in normal oral mucosa (0/8); The Caspase-3 expression were 30 among 40 cases, the positive rate was 75% in oral squamous cell carcinoma, and was 100% in normal oral mucosa (8/8). By statistical analysis, we have found there are differences between oral squamous cell carcinoma and normal oral mucosa. After 12C6+ ion irradiation with different doses,Survivin expression was statistically significant (P<0.05) compared with the OSCC group, but the differences of Caspase-3 expression did not occurred. The 12C6+ ion irradiation group compared with OSCC group was not statistically significant (P>0.05).Conclusions:1 The 0.3% concentration of DMBA acetone solution is more suitable for the formation of oral squamous cell carcinoma model in Golden Hamster in the short term. This method is benefit to shorten the feeding cycle, reduce costs.2 Exposed with different doses of heavy ion beam irradiation, there are some changes of content in trace elements of serum, which are of clinical significance.3 12C6+ ion irradiation can reduce the expression of Survivin, indirectly raise the activity of Caspase-3. It reveals to us the 12C6+ ion irradiation may play a critical role in the regulation of the process of cell apoptosis.