SEQUENTIAL MAST-CELL INFILTRATION AND DEGRANULATION DURING EXPERIMENTAL CARCINOGENESIS

Mast cell density, distribution, and ultrastructure were studied by light and electron microscopy in hamster buccal pouches undergoing chemically induced carcinogenesis. Epidermoid carcinomas in the pouches were induced by three topical applications per week of 0.5% 7,12-dimethylbenz[a]anthracene (DMBA) in oil using a brush. Four experimental, DMBA-treated and two normal, untreated hamsters were sacrificed after 8, 10, 12, 14, and 16 weeks. After 8 weeks of DMBA treatment, the epithelium showed the pathological signs of dysplasia and hyperkeratosis. In the dermis an increased number of mast cells were evident, some of which showed degranulation. A few mast cells had started to migrate upwards towards the dysplastic epithelium after 10 weeks of DMBA treatment. Rapid degranulation was also apparent in some mast cells. These processes of upward migration and degranulation continued progressively during the 12- and 14-week periods of DMBA application in correlation with the progression of the tumor. By 16 weeks of treatment with the carcinogen, more mast cells had migrated closer to the invasive carcinoma, and many had degranulated. In the connective tissue mast cells were fully packed with many granules, and some mast cells were in proximity to macrophages and eosinophils. Our observations demonstrate that there is a positive correlation between developing carcinomas and mast cell density. Mast cell migration towards the carcinoma and degranulation were also evident.