2-Acetylaminofluorene-produced selective cytotoxic damage of a ductal compartment and its repair in the submandibular gland of rats

Salivary glands of rodents are rarely affected with spontaneous and induced malignancies. This may be linked with low physiologic cell renewal and the infrequency of cytolethal actions by xenobiotics. The genotoxic 2-acetylaminofluorene, carcinogenic for other organs, causes acute damage in salivary ducts. In the submandibular glands the damage is limited to the granulated convoluted tubules. They produce and release regulatory peptides including epidermal growth factor and nerve growth factor. The partial chemical sialoadenectomy is repaired by sequential cell proliferation in the basal cell layer of interlobular ducts and in dilated intralobular ducts (day 4 and 6), in intermediate duct-like structures (day 6 and 8), and lastly in acini (day 8 and 12). This is associated with a transient loss of structural characteristics of striated ducts and acini (up to day 6) and of the immunoreactivity for S-100 protein (up to day 4). Actin immunoreactivity at the acinar base is increased from day 6 to 20. Analogous to the late postnatal differentiation of the granulated convoluted tubules, their structural characteristics and immunoreactivity for epidermal growth factor do not recover within 20 days. The acute lesion of the endocrine ductal segment is suggested to be causally involved with other systemic effects following treatment with 2-acetylaminofluorene. First, hypophagia with loss of body, liver and thymus weight may result from disturbed saliva production. Second, previous studies have shown a mitotic burst of the biliary epithelium and bloodborne lymphocyte-stimulating activities. Either effect could be brought about by regulatory peptides (see above), probably after elevated circulatory release from necrotic granulated convoluted tubules.