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Changes in Secretory Cells during Early Stages of Experimental Carcinogenesis in the Rat Submandibular Gland¹

Veterans Administration Hospital and The University of Michigan, Ann Arbor, Michigan 48105

Previous studies have shown that the local injection of 7, 12-dimethylbenz(a)anthracene induces largely squamous cell carcinoma in the rat submandibular gland. This study describes cytological changes that occur initially in the secretory cells of the rat submandibular gland following the injection of 7, 12-dimethylbenz(a)anthracene. One of the most striking features noted early in injected glands is the appearance of duct-like structures, which appear to form by metaplastic transformation of secretory cells, mostly acinar cells. These structures are first noted at about 2 weeks after the injection, well before first signs of cancer appear at about 14 weeks, and increase continuously in number. Radioautographic studies of injected glands have indicated that a large number of acinar cells and cells of the duct-like structures become labeled with tritiated thymidine, suggesting an increased mitotic activity in these cells. The fine structural alterations seen in cells of the duct-like structures and in acinar cells undergoing metaplastic transformation are characteristic of those associated frequently with depressed protein synthesis. The secretory cells of the control gland do not reveal the alterations described above, suggesting that the changes in the secretory cells of the experimental gland are related either directly or indirectly to the presence of 7, 12-dimethylbenz(a)anthracene and may represent an initial event in carcinogenesis.

¹ This is Paper 1 of a series entitled "Experimental Carcinogenesis in the Rat Submandibular Gland." Veterans Administration Research Project 4927:01.

Received 9/19/73. Accepted 5/10/74.