2-ACETYLAMINOFLUORENE-PRODUCED SELECTIVE CYTOTOXIC DAMAGE OF A DUCTALCOMPARTMENT AND ITS REPAIR IN THE SUBMANDIBULAR-GLAND OF RATS

Salivary glands of rodents are rarely affected with spontaneous and in duced malignancies. This may be linked with low physiologic cell renew al and the infrequency of cytolethal actions by xenobiotics. The genot oxic 2-acetylaminofluorene, carcinogenic for other organs, causes acut e 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 growt h factor. The partial chemical sialoadenectomy is repaired by sequenti al cell proliferation in the basal cell layer of interlobular ducts an d in dilated intralobular ducts (day 4 and 6), in intermediate duct-li ke structures (day 6 and 8), and lastly in acini (day 8 and 12). This is associated with a transient loss of structural characteristics of s triated 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 differ entiation of the granulated convoluted tubules, their structural chara cteristics and immunoreactivity for epidermal growth factor do not rec over within 20 days. The acute lesion of the endocrine ductal segment is suggested to be causally involved with other systemic effects follo wing treatment with 2-acetylaminofluorene. First, hypophagia with loss of body, liver and thymus weight may result from disturbed saliva pro duction. Second, previous studies have shown a mitotic burst of the bi liary epithelium and bloodborne lymphocyte-stimulating activities. Eit her effect could be brought about by regulatery peptides (see above), probably after elevated circulatory release from necrotic granulated c onvoluted tubules.