THE PATHOBIOLOGY OF SALIVARY-GLAND .3. PCNA-LOCALIZATION OF CYCLING CELLS INDUCED IN RAT SUBMANDIBULAR-GLAND BY LOW-DOSE X-RADIATION

Application of ionizing radiation to adult rat major salivary glands t ested tenets of the bicellular reserve cell hypothesis for the inducti on of salivary gland tumors, namely, that stem cells are preferentiall y located to luminal cells of the intercalated duct and basal cells of the excretory duct in normal salivary glands. The effect of a single, low dose (3000 cGy) of x-radiation administered to the parotid and su bmandibular glands was followed with the use of immunocytochemistry an d an antibody to the cell cycle-related protein proliferating cell nuc lear antigen to detect the kinetics and localization of cycling cells up to 15 days postirradiation. Maximal responses occurred in acinar ce lls (12.6-fold increase) of submandibular glands on day 7 postirradiat ion. Similar but less dramatic concurrent increases in proliferating c ells were evident in intercalated (3.4-fold) and striated (2.2-fold) d uct cells, but little response was seen in basal or luminal cells of s ubmandibular gland excretory ducts. A limited but maximal proliferativ e response again occurred on day 7 in the parotid gland. Neither in th e steady state nor irradiated submandibular gland was there evidence o f specific stem (''reserve'') cells associated with the intercalated o r excretory ducts. It appears unnecessary to invoke stem cells in a mo del of cellular proliferation in salivary glands. Therefore current co ncepts of salivary gland tumorigenesis require modification because al l cell types, including acinar cells, are at risk in the carcinogenic process.