COLCHICINE-INDUCED CELL-DEATH AND PROLIFERATION IN THE OLFACTORY EPITHELIUM AND VOMERONASAL ORGAN OF THE MOUSE

The cytotoxic agent colchicine induced apoptotic cell death and subseq uent regeneration in the mouse olfactory epithelium and vomeronasal or gan. The TUNEL method revealed the presence of many apoptotic bodies i n the middle to basal region of the septal olfactory epithelium and vo meronasal organ near the boundary of the respiratory epithelium at 1 d ay after a single i.p. injection of colchicine (4 mg/kg b.w.). In some regions of the third and the fourth nasal turbinates, massive apoptos is was observed in the olfactory epithelium. Electron micrographs of t he septum showed that immature olfactory cells and globose basal cells were killed by the colchicine and had been phagocytized by the suppor ting cells and macrophages. In the vomeronasal organ, immature sensory cells and precursors died in response to the colchicine. In response to cell death, active proliferation of precursor cells (globose basal cells) and subsequent regeneration of olfactory cells occurred in the olfactory epithelium and vomeronasal organ. Incorporation of the mitot ic tracer BrdU by precursor cells reached its peak at 4 days after col chicine treatment in the vomeronasal organ, and at 6 to 7 days in the olfactory epithelium; however, in some regions in the third and the fo urth nasal turbinates, where many olfactory cells and globose basal ce lls had died by colchicine effect, the regeneration did not occur even in 1 month, forming the epithelium of only supporting cells and horiz ontal basal cells. In the next month, these regions became normal olfa ctory epithelium. This suggests that the globose basal cells in the su rrounding normal olfactory epithelium might invade these regions to gi ve rise to the olfactory cells.