In conclusion, exposure of human solid tumor cells to ionizing radiation induces numerical aberrations of the centrosomes, multipolar spindle formation, and micro- or multinucleated phenotypes characteristic of mitotic cell death. The origin of supernumerary centrosomes in response to radiation is unknown, but possible mechanisms include dissociation between centrosome duplication and DNA replication cycles coupled with the loss of a centrosome-intrinsic mechanism to block reduplication, failure of cytokinesis associated with polyploidization, and centro-some fragmentation. Although there is no direct evidence to indicate that centro-some anomalies contribute to the killing of tumor cells after irradiation, supernumerary centrosomes or centrosome-like structures that retain microtubule-nucleat-ing activity provide an attractive model for radiation-induced nuclear fragmentation and subsequent cell death. A better understanding of the origins and consequences of centrosome anomalies in response to radiation may have important clinical implications. For example, if such centrosome phenotypes correlate with overall cell killing after radiation treatment, the extent of centrosome aberrations may be used as an indicator of treatment response and as a prognostic marker. It is also important to identify and characterize the molecular pathways associated with the induction of abnormal centrosome phenotypes after irradiation. Identification of such pathways could lead to the development of novel centrosome-related strategies to enhance the efficacy of current treatment regimens for cancer patients.
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