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Enhanced Poly(adenosine diphosphate ribose) Polymerase Activity and Gene Expression in Ewing's Sarcoma Cells¹

Departments of Radiation Medicine and Biochemistry, Georgetown University Medical Center, Washington, DC 20007

Ewing's sarcoma (ES) is a highly malignant childhood bone tumor and is considered curable by moderate doses of radiotherapy. The addition of chemical inhibitors of the activity of the nuclear enzyme poly(adenosine diphosphate ribose) [poly(ADPR)] polymerase to ES cells in culture results in increased cell killing, a phenomenon called "inhibitor sensitization." Since poly(ADPR) polymerase is thought to be associated with DNA repair, it has been suggested that ES cells and other inhibitor-sensitized cells may have a reduced capacity for polymer synthesis resulting in deficient postirradiation recovery. We present here the unexpected observation that in comparison to other cell lines tested, ES cells exhibit a high enzyme activity, higher constitutive levels of the protein, and elevated levels of its mRNA transcript for poly(ADPR) polymerase. No gross amplifications or rearrangements of the gene were observed; however, regulation of poly(ADPR) polymerase in these tumor cells takes place at the level of the gene transcript.

¹ This work was supported in part by grants from the American Cancer Society and the NIH.

² To whom requests for reprints should be addressed.

Received 12/15/88. Revised 9/27/89. Accepted 10/ 3/89.

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