Enhanced poly(adenosine diphosphate ribose) polymerase activity and gene expression in Ewing's sarcoma cells.
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.
Prasad
S C
SC
Department of Radiation Medicine, Georgetown University Medical Center, Washington, DC 20007.
Thraves
P J
PJ
Bhatia
K G
KG
Smulson
M E
ME
Dritschilo
A
A
D015152:Blotting, Northern; D015139:Blotting, Southern; D015153:Blotting, Western; D002460:Cell Line; D002470:Cell Survival / Q000528:radiation effects; D006367:HeLa Cells / Q000201:enzymology; D006801:Humans; D007700:Kinetics; D009693:Nucleic Acid Hybridization; D011065:Poly(ADP-ribose) Polymerases / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D015183:Restriction Mapping; D012512:Sarcoma, Ewing / Q000201:enzymology* / Q000235:genetics; D014158:Transcription, Genetic; D014407:Tumor Cells, Cultured / Q000166:cytology / Q000201:enzymology* / Q000528:radiation effects
D012333:RNA, Messenger; D011065:Poly(ADP-ribose) Polymerases