| Background:There is not very good therapeutic to Malignancy all along, and oral carcinoma is no exception. The rate of oral carcinoma ranks the 6th in all cancers, and it occurs more and more in both developed and developing countries in recent years. Therapeutics of Oral Carcinoma is limited to operation, radiotherapy chemotherapeutics, and united treatment of two or more of the previous methods currently, some of them have serious adverse effect and toxic effect, some of them cause structure defect of economy and dysfunction very easily, which seriously worsen the life quality of patients. If patients can be found with Oral Carcinoma in time and get an early treatment, they will recover better. So the early diagnosis, discovery of Oral Carcinoma and its pathogenesis are very importantObjective:This experiment is an immunohistochemistry research of Grp78 and GADD153 on the palatine mucosa of mice oral carcinoma induced by 4NQO with the purpose of finding out the action mechanism of Grp78 and GADD153 in the cancerization of oral mucosa in order to provide help to an early discovery and gene treatment of oral carcinoma.Methods:70 8-week mice, each weighs about 200g (all come from Henan Animal Experiment Center).63 of them:experimental group, the rest 7:control group. Experiment Condition:16℃-22℃, feel them with delicate compound feedstuff (bought from Henan Animal Experiment Center), natural light-dark cycles in 24 hours, each 7 mice in one cage, with sawdust at the bottom of cages and change new sawdust for 3 times every week, change drinking-water and add feedstuff every day. Spread 4NQO distilled water with a consistence of 0.5% to the palate of all the experimental mice, once two days for a consecutive 28 weeks, do nothing to the control group.In the process, pick up 9 from experimental group and one from the control group randomly in the 4th,8th,12th,16th,20th,24th and 28th week, make them dead by disjointing their necks, observe them with eyes and cut some samples, fasten them with 10% formalin, embedded them with olefin, slice up 3 pieces of 4μm consecutively and do normal H-E staining, then observe the pathological changes under a Light microscope and record the numbers of the changes. Pathological changes of mice are divided into simple hyperplasia, light dysplasia, moderate dysplasia, severe dysplasia, carcinoma in situ, stage invasive carcinoma and cancer. All the above exemplars were analyzed by two experienced pathological doctors with double-blinded method and they came out with the same conclusion. Slices dealt with in Immunohistochemistry methods are also 4μm consecutive slices, stain the Grp78 and GADD153 fall the exemplars in immunohistochemistry method, account each of their average optical of Grp78 and GADD153 protein, deal with the date medically and statistically with SPSS13.0, do ANOVA analysis of which the standard isα=0.05 and do correlation analysis with Spearman Correlation Analysis.Results:1.Build mice carcinoma animal model:Under the combined effect of time and carcinogen,100% of the mice's palatine membrane cells are simple hyperplasia at the 4th week,55.6% are simple hyperplasia and 44.4% are mild hyperplasia at the 8th week,22.2% are simple hyperplasia,55.6% are moderate hyperplasia and 22.2% are severe hyperplasia at the 12th week,44.4% are moderate hyperplasia,55.6% are severe hyperplasia at the 16th week; 11.1% are moderate hyperplasia 77.8% are severe hyperplasia and 11.1% are carcinoma in situ at the 20th week; 55.6% are severe hyperplasia,33.4% are carcinoma in situ and 1 invasive well differentiated carcinoma appears at the 24th week; cancers are the main phenomena at the 28th week with 2 cancer in site and 7 carcinoma.2.The average optical density of positive cells of Grp78 protein in normal mucous, simple hyperplasia, mildly proliferation mucous, moderately proliferation mucous, severely proliferation mucous and oral carcinoma organizations are 98.75±8.06,99.08±7.61,112.67±6.39,131.21±7.09,35.61±19.16和148.58±7.18,, In all proliferation mucous, The average optical density of positive cells in the GRP78 protein mildly, moderately and severely proliferation mucous heighten gradually, and they have significant differences(P<0.05), except moderately proliferation mucous and severely proliferation.3.The average optical density of positive cells of GADD153 protein in normal mucous, simple hyperplasia, mildly proliferation mucous, moderately proliferation mucous, severely proliferation mucous and oral carcinoma organizations are 103.53±13.8,107.17±11.61,141.60±5.30,125.80±9.58,118.87±8.09,105.13±8.37. normal mucous and oral carcinoma mucous,normal mucous and simple hyperplasia,simple hyperplasia and oral carcinoma mucous were no significant difference (P>0.05), Other proliferation of mucosa comparison between two are significantly different (P<0.05). The average optical density of positive cells in the GADD153 protein in mild, moderate, and severe proliferation of mucosa decreased gradually but statistically have significance.4.In the correlation analysis of the expression of Grp78 and GADD153, correlation coefficient r=-0.638,P=0.000<0.05 indicate that Grp78 and GADD153 have negative correlationConclusions:1. Build mice plate carcinoma animal model successfully. The cancerization of palatine mucous is a dynamic change from simple hyperplasia, mild hyperplasia, moderate hyperplasia, severe hyperplasia, carcinoma in situ, to stage invasive carcinoma.2.Grp78 proteins don't express or slightly express in normal mucous membranes, but they express more highly in turn in dysplasia mucous membranes and oral carcinoma mucus. which indicates that Grp78 proteins take part in the occurrence and development of oral carcinoma, It can also be treated as targets for the next research direction.3. GADD153 proteins don't express or slightly express in normal mucous membranes, and they express in mild hyperplasia, moderate hyperplasia, severe hyperplasia of the mucosa and oral cancer tissues decreased gradually, which indicates that GADD153 take part in the occurrence and development of oral carcinoma.4. Inspecting the expression of Grp78 and GADD153 at the same time can make us discover oral carcinoma at its early stage and provide help to gene treatment of the oral carcinoma.
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