Acinar Cell Hypertrophy, Proliferation and Cell Death in Rat Submandibular Glands Induced by Long-Term Isoproterenol Administration

Abstract

The purpose of this study was to elucidate the relationship between cell proliferation and cell death of submandibular gland (SMG) acinar cells in rats treated with the β-adrenergic secretagogue isoproterenol (IPR) which elicits massive growth of salivary glands. We analyzed this process using computerized imaging analysis, 5-bromo-2'-deoxyuridine (BrdU) immunohistochemical staining, the terminal deoxyribonucleotidyl transferase (TdT)-mediated-deoxyuridine triphosphate (dUTP)-biotin nick end labeling (TUNEL) method and ultrastructural observations for 10 days of IPR treatment and for 3 weeks thereafter. Proliferation of acinar cells occurred at days 2 and 3 of IPR administration, and acinar cell hypertrophy continued during the entire 10-day treatment period. Numerous TUNEL-positive cells and vesicular structures were found in the acinar area by day 3 post-IPR administration. Ultrastructurally, vacuolated structures that resembled "degenerating apoptotic bodies" were located in and between the acinar cells. A different type of cell death, which was associated with an electron-lucent and edematous cytoplasm but not with mitochondrial lysis or cell membrane destruction, was also recognized in the acinus. It is suggested that this other type of cell death may correspond to "secondary necrosis".