Abstract | BACKGROUND: METHODS: Quantitative PCR was used to measure PARP-1, -2, -3 and PARG mRNA levels and western blotting for PARP-1 protein expression and ADP-ribose polymer formation after exposure of cells to doxorubicin, a topoisomerase II poison. DNA repair capacity was assessed using an in vitro DNA lesion excision/synthesis assay and the effects on cell killing of the PARP inhibitor ABT-888 alone and in combination with ionizing radiation using clonogenic survival. RESULTS: Although a wide range in expression of the PARPs and PARG was found correlations between PARP-1 and PARP-2 mRNA levels and PARP-1 mRNA and protein levels were noted. However these expression profiles were not predictive of PARP activity in the different cell lines that also showed variability in excision/synthesis repair capacity. 4 of the 7 lines were sensitive to ABT-888 alone and the two lines tested showed enhanced radiosensitivity in the presence of ABT-888. CONCLUSIONS:
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Authors | Clément Guillot, Vincent Favaudon, Zdenko Herceg, Charlotte Sagne, Sylvie Sauvaigo, Philippe Merle, Janet Hall, Isabelle Chemin |
Journal | BMC cancer
(BMC Cancer)
Vol. 14
Pg. 603
(Aug 20 2014)
ISSN: 1471-2407 [Electronic] England |
PMID | 25139788
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Benzimidazoles
- Radiation-Sensitizing Agents
- veliparib
- Doxorubicin
- Poly(ADP-ribose) Polymerases
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Topics |
- Benzimidazoles
(pharmacology)
- Carcinoma, Hepatocellular
(genetics, therapy)
- Cell Line, Tumor
- Cell Survival
(drug effects, radiation effects)
- DNA Repair
(drug effects, radiation effects)
- Doxorubicin
(pharmacology)
- Drug Screening Assays, Antitumor
- Gene Expression Regulation, Neoplastic
(drug effects, radiation effects)
- Hep G2 Cells
- Humans
- Liver Neoplasms
(genetics, therapy)
- Poly(ADP-ribose) Polymerases
(genetics, metabolism)
- Radiation, Ionizing
- Radiation-Sensitizing Agents
(pharmacology)
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