OCCURRENCE OF APOPTOTIC DNA FRAGMENTATION IN QUIESCENT AND PROLIFERATING CELLS IN HUMAN ENDOMETRIAL ADENOCARCINOMA TISSUES AND THE INFLUENCE OF APOPTOSIS-SUPPRESSING EFFECTS OF BCL-2 PRODUCTS

In situ estimation of DNA fragmentation by the nick end labelling (NEL ) method, and immunohistochemical examination of Ki-67 proliferative a ntigen and bcl-2 products in human endometrial adenocarcinoma tissues were performed to provide answers to the following two questions; a) d oes apoptotic DNA fragmentation occur specifically in quiescent cells or in proliferating cells or randomly in both?, b) does the bcl-2 prod uct exert its apoptosis-suppressing effects differentially on carcinom a cells depending on their cell cycle condition?. Serial sections, one micrometer in thickness, from formalin-fixed and paraffinembedded tis sues of 9 cases of human endometrial adenocarcinoma were examined. Apo ptotic DNA fragmientation was observed in both quiescent (Ki-67 negati ve) and proliferating (Ki-67 positive) cells. Bcl-2 product-positive t umor cell islands tended to be NEL negative, although a few but non-ne gligeable number of carcinoma cells, including both Ki-67 positive and negaitive ones, were NEL positive. These results indicate chat, at le ast in human endometrial adenocarcinomas, apoptotic DNA fragmentation and bcl-2 product-independent (DNA) fragmentation occurs non-specifica lly with respect to the cell proliferation status. Further, the result s suggest an altered regulation of cell death processes in human solid tumor tissue in vivo.