APOPTOSIS IN THE HUMAN INNER-EAR - DETECTION BY IN-SITU END-LABELING OF FRAGMENTED DNA AND CORRELATION WITH OTHER MARKERS

The aim of this study was to obtain baseline data on the recently desc ribed special form of single cell death, apoptosis, in normal human in ner ears. For this purpose, in situ end-labeling of the fragmented DNA was applied, in conjunction with apoptosis-related markers, to detect cellular elements showing programmed cell death in decalcified and pa raffin-embedded tissues. Over 20 specimens were analyzed which were ob tained from autopsy cases with no history of acoustic lesions confirme d by histopathology. Based on staining results, we saw no apoptotic si gns in the majority of normal adult inner ears. An apoptotic cell capt ured in the Reissner's membrane of the cochlea from an old patient may , however, indicate an age-related subtle cell loss with the process o f apoptosis. Nevertheless, the fact that more apoptosis was not found in our cases suggests that this phenomenon does not contribute signifi cantly to the tissue homeostasis in the adult inner ear under normal c onditions. These data are in accordance with our immunohistochemical f indings on the p53 nucleoprotein, and proliferating cell nuclear antig en expression since there was no staining in any of the cellular eleme nts, including the mesenchymal cells. This reflects a stationary and s table condition of cells of the vestibular and the cochlear structures , probably to maintain their integrity and the fine sensory functions. As opposed to the above findings, during inner ear development, the e pithelial cells lining the cochlear lumen, the ossifying cartilage of the temporal bone, and the mesenchymal cells show different degrees of proliferation in combination with single cell death as signs of matur ation of the vestibular and the cochlear apparatus. In addition, apopt osis has been demonstrated in cells of the cochlear stria vascularis f rom an adult patient treated with high doses of cisplatin, vinblastine and bleomycin prior to death. Furthermore, a wide range of apoptosis could be induced experimentally in a normal ear by an external perfusi on of actinomycin D (ActD), which is known to produce programmed cell death in many cell types of different origins. The potential role of c ytostatic agents in the apoptotic process of the inner ear needs, howe ver, to be confirmed in large-scale specimens from patients treated wi th genotoxins. The fact, however, that apoptotic cells are also seen i n association with ActD indicates that the fine sensory structure of t he cochlea may also be a target for certain chemotherapeutic agents wh en administered in high doses. (C) 1998 Elsevier Science B.V.