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A combination of antiapoptotic/antinecroptotic inhibitors protects nccit cells from gamma-irradiation-induced cell death.

Authors
Huang-Z; Greenberger-J; Kagan-V; Bayir-H
Source
Toxicologist 2012 Mar; 126(Suppl 1):441
NIOSHTIC No.
20040661
Abstract
Irradiation-induced cell death includes apoptotic and necroptotic (or programmed necrosis) pathways. Therefore, a search for radiomitigators with the delayed action against acute radiation injury due to radionuclide release in terrorist acts may be based on a combination of antiapoptotic and antinecroptotic inhibitors. Here we used a cocktail that included a pan-capase inhibitor, Z-VAD-fmk, and necrostatin- 1, a specific inhibitor of receptor interacting protein-1 (RIP-1) - a key protein in necroptosis - and assessed their protective effects against irradiation-induced (4 Gy) death of embryonic carcinoma NCCIT cells (5 days after irradiation). We found that a combination of Z-VAD-fmk (50-100 microM) plus necrostatin-1 (20 microM) showed significant radiomitigative effect - from 33.5%~61.9% in NCCIT cells (treatment at 30 min after the irradiation exposure). No significant protection was afforded by either of these compounds alone. Our results suggest that necroptosis inhibitors - along with other therapeutic modalities - may be promising as mitigators against late radiation-induced cell death.
Keywords
Cytology; Cell-damage; Cell-morphology; Cellular-function; Laboratory-animals; Molecular-biology; Cell-metabolism; Radiation; Radiation-injury; Pathology; Embryotoxicity; Carcinomas
Publication Date
20120301
Document Type
Abstract
Funding Type
Grant
Fiscal Year
2012
NTIS Accession No.
NTIS Price
Identifying No.
Grant-Number-R01-OH-008282; B04252012
ISSN
1096-6080
Source Name
The Toxicologist. Society of Toxicology 51st Annual Meeting and ToxExpo, March 11-15, 2012, San Francisco, California
State
PA; CA
Performing Organization
University of Pittsburgh at Pittsburgh
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