Mitotic catastrophe as a prestage to necrosis in mouse liver cells treated with Helicobacter pullorum sonicates.

Helicobacter pullorum infections have been associated with several enterohepatic diseases, but the mechanism of action is currently undefined. The present study was therefore set up to investigate possible cytotoxic effects of this pathogen on liver cells. A mouse hepatic cell line was exposed to H. pullorum sonicate and cytotoxicity was observed for all isolates after incubation for 72 h. Features characteristic for mitotic catastrophe characterized by chromatin condensation, formation of multinuclear distended cells and micronucleation, were recorded. In addition, intranuclear pseudoinclusions were seen in sonicate-treated cells. Finally, cells exposed to sonicate eventually underwent cell death with the morphological features of necrosis, which occurred without activation of caspase-3. The toxic factor involved in the cytotoxic activity proved to be soluble, trypsin-sensitive and stable at 56 degrees C and at -70 degrees C with a molecular weight to be over 50 kDa. The current study shows for the first time that H. pullorum causes mitotic catastrophe resulting in primary necrosis in mouse hepatocytes. (c) 2009 Wiley-Liss, Inc.