Changes in sub-nuclear structures and functional perturbations: implications for radiotherapy.

J. L. Roti Roti*, D. Gius, R. P. VanderWaal, M. Xu

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

1 Scopus citations

Abstract

The eukaryotic cell nucleus is required to accomplish its functions (e.g., replicating transcription, DNA repair, hmRNA processing, etc.) within the context of a highly organized structure [Wei X, Samarabandu J, Devdhar RS, Siegel AJ, Acharya R, Berezney R. 1998. Science 281:1502-1506.], since many cancer-therapeutic modalities utilize the nucleus as target for a cytotoxic outcome. A better understanding of the organizational disruption of sub-nuclear structures and subsequent loss of nuclear function is the key to knowing both the mechanism of action of, and the basis of cellular sensitivity to, therapeutic agents such as ionizing radiation. With this prospect, we examine four examples in which changes in specific nuclear structures or functions lead to significant therapeutic end points, e.g. cell death, radiosensitization, or the intrinsic radioresistance of tumor cells. The inter-relationships delineated in these examples provide a paradigm that delineates a relationship between disruption of nuclear organization, loss of function and a point of intervention that affects a therapeutic outcome. The examples specifically address issues related to radiation and thermal therapy. However, the concepts that result from these studies are translatable to other cancer therapeutic modalities. In addition, the results echo a basic principle that proper nuclear organization is critical to the maintenance of cellular viability and genomic stability. J. Cell. Biochem. Suppl. 35:142-150, 2000.

Original languageEnglish (US)
Pages (from-to)142-150
Number of pages9
JournalJournal of cellular biochemistry. Supplement
VolumeSuppl 35
StatePublished - Jan 1 2000

ASJC Scopus subject areas

  • Medicine(all)

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