|Budget Amount *help
¥2,300,000 (Direct Cost : ¥2,300,000)
Fiscal Year 1996 : ¥1,100,000 (Direct Cost : ¥1,100,000)
Fiscal Year 1995 : ¥1,200,000 (Direct Cost : ¥1,200,000)
Proliferating cells and its immunohistochemical properties were evaluated during experimental carcinogenesis induced by DMBA containing sponge-pellet implantation and after duct-ligation of rat submandibular glands (SMGs).
In the normal rat SMGs, proliferating cells were very very few, epidermal growth factor (EGF) was confined to the granules in granular convoluted tubules (GCTs), S-100 alpha was found in pillar and transition cells in GCT and striated duct (SD) and excretory duct (ED), K8.12 keratin, basic fibroblast growth factor (bFGF), and c-erbB-2 oncoprotein were found in SD and ED,and laminin existed at basement membrane of glandular epithelia and blood vessels.
Two to three weeks after DMBA/sponge implantation, small clusters of proliferating cells were observed in necrotic oedematous area surrounding DMBA/sponge and duct-like structures and dilated ductal segments with small numbers of proliferating cells (10-25%) were found in inflammatory area surrounding necrotic oedematous
area. These components showed positive for K8.12 keratin, S-100 alpha protein, bFGF,and c-erbB-2 oncoprotein and negative for EGF.Four to six week after DMBA/sponge implantation, keratinized epithelium extended surrounding DMBA/sponge like a cyst and some proliferating cells were observed in basal and parabasal area of cystic epithelium (* 27%). Histological and immunohistochemical features of cystic epithelium were similar to those of oral leucoplakias and c-erbB-2 oncoprotein was observed in this lesion. Squamous cell carcinomas (SCC) arose 8 to 12 weeks after DMBA/sponge implantation. Proliferating cells were observed mainly in basal and parabasal area of SCC and the frequency of proliferating cells were more than 30%. C-erbB-2 oncoprotein was observed also in the SCC.Invasive growth feature of tumor cells with breakages of basement membrane were some times found in after 12 weeks speciments.
In the duct-ligated SMG,proliferating cells were increased in duct-like structures and the peak of the PCNA labeling was about 50% at the third day and then gradually decreased into 10% at the 21st day of experiment. Histological and immunohistochemical findings of duct-like structures in duct-ligated SMG were similar to those of duct-like structures which appeared during carcinogenesis. In unligated gland of experimental animals showed proliferation activity in acinar cells and its peak was at the second day (* 20%) and rapidly decrease into normal level at the 10th day of experiment.
These results suggested that in case of acceleration of secretory function of SMG,secretory cells may proliferate as for the functional adaptation. However, in case of damage, ductal segments have more potential for proliferation and these cells may be the major participant cells during glandular regeneration and possibly source in the histogenesis of the majority of salivary gland tumors. Furthermore, apperance of c-erbB-2 oncoprotein in ductal segment and tumor cells, and EGF is accumulated in GCT,these findings may influences of rapidly carcinogenesis compared to another organs. Less