Selective elimination of acentric double minutes from cancer cells through the extrusion of micronuclei.

Several lines of evidences from us or other authors had shown that tumor cells revert their phenotypes and differentiate by the elimination of oncogenes amplified on the acentric double minutes (DMs). The selective incorporation of DMs into the cytoplasmic micronuclei was thought to be involved in this elimination, however, the mechanism by which the content of micronuclei was eliminated from the cells remains to be discovered. In this report, we show the finding and the characterization of the extruded micronuclei in the culture fluid of human COLO 320DM tumor line, and suggest that the extrusion of micronuclei mediates the selective elimination of DMs. The extracellular micronuclei enriched with DMs had an apparently normal cytoplasmic membrane, decondensed chromatin and nuclear lamin protein, and their DNA did not suffer any extensive degradation. These characteristics were closely related to their cytoplasmic counterpart and clearly differentiated from the apoptotic bodies. We also developed a method for purifying the extracellular micronuclei. In this paper, the implications of the micronuclear extrusion are discussed.