Radiation protection by a new chemical entity, Ex-Rad™: Efficacy and mechanisms

Radiation Research

Volumn 171, Issue 2, 2009, Pages 173-179

  Ghosh, Sanchita P ^a,e   Perkins, Michael W ^a   Hieber, Kevin ^a,e   Kulkarni, Shilpa ^a,e   Kao, Tzu Cheg ^a   Premkumar Reddy, E ^b   Ramana Reddy, M V ^b   Maniar, Manoj ^c   Seed, Thomas ^d   Sree Kumar, K ^a  

^a UNIFORMED SERVICES UNIVERSITY OF THE HEALTH SCIENCES   (United States)

^b TEMPLE UNIVERSITY SCHOOL OF MEDICINE   (United States)

^c Onconova Thempeutics Inc   (United States)

^d RADIATION EFFECTS RESEARCH FOUNDATION   (Japan)

^e Military Medicine Inc   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

4 CARBOXYSTYRYL 4 CHLOROBENZYLSULFONE; ABELSON KINASE; COBALT 60; DNA; EX RAD; PHOSPHOTRANSFERASE INHIBITOR; PROTEIN BAX; PROTEIN P21; PROTEIN P53; PROTEIN P73; SMALL MOLECULE KINASE INHIBITOR; UNCLASSIFIED DRUG;

ANIMAL MODEL; ANIMAL TISSUE; APOPTOSIS; ARTICLE; C3H MOUSE; CANCER CELL; CANCER CELL CULTURE; CANCER RADIOTHERAPY; CANCER SURVIVAL; CELL CYCLE; CELL STRAIN AG1522; CELL STRAIN HFL 1; COMET ASSAY; CONTROLLED STUDY; DNA DAMAGE; DRUG EFFICACY; DRUG MECHANISM; ENDOTHELIUM CELL; FEMALE; GAMMA IRRADIATION; GAMMA RADIATION; GEL ELECTROPHORESIS; HUMAN; HUMAN CELL; IN VITRO STUDY; LUNG FIBROBLAST; MALE; MOUSE; NONHUMAN; PRIORITY JOURNAL; RADIATION DOSE; RADIATION INJURY; RADIATION PROTECTION; SKIN FIBROBLAST; UMBILICAL VEIN; WESTERN BLOTTING;

ANIMALS; BLOTTING, WESTERN; CELLS, CULTURED; COMET ASSAY; DNA DAMAGE; DOSE-RESPONSE RELATIONSHIP, RADIATION; DOWN-REGULATION; HUMANS; MALE; MICE; MICE, INBRED C3H; RADIATION-PROTECTIVE AGENTS; SULFONAMIDES;

MUS;

EID: 59649092946     PISSN: 00337587     EISSN: None     Source Type: Journal    
DOI: 10.1667/RR1367.1     Document Type: Article

References (28)

1. P. Fei and W. S. El-Deiry, P53 and radiation responses. Oncogene 22, 5774-5783 (2003).
2. H. J. Mauceri, N. N. Hanna, M. A. Beckett, D. H. Gorski, M. J. Staba, K. A. Stellato, K. Bigelow, R. Heimann, S. Gately and R. R. Weichselbaum, Combined effects of angiostatin and ionizing radiation in antitumour therapy. Nature 394, 287-291 (1998).
3. V. Garaj-Vrhovac and N. Kopjar, The alkaline comet assay as bio-marker in assessment of DNA damage in medical personnel occupationally exposed to ionizing radiation. Mutagenesis 18, 265-271 (2003).
4. V. J. McKelvey-Martin, M. H. Green, P. Schmezer, B. L. Pool-Zobel, M. P. De Meo and A. Collins, The single cell gel electrophoresis assay (comet assay): a European review. Mutat. Res. 288, 47-63 (1993).
5. N. P. Singh, M. T. McCoy, R. R. Tice and E. L. Schneider, A simple technique for quantitation of low levels of DNA damage in individual cells. Exp. Cell Res. 175, 184-191 (1988).
6. Z. M. Yuan, Y. Huang, T. Ishiko, S. Kharbanda, R. Weichselbaum and D. Kufe, Regulation of DNA damage-induced apoptosis by the c-Abl tyrosine kinase. Proc. Natl. Acad. Sci. USA 94, 1437-1440 (1997).
7. C. A. Jost, M. C. Marin and W. G. Kaelin, Jr., p73 is a simian [correction of human] p53-related protein that can induce apoptosis. Nature 389, 191-194 (1997).
8. M. Kaghad, H. Bonnet, A. Yang, L. Creancier, J. C. Biscan, A. Valent, A. Minty, P. Chalon, J. M. Lelias and D. Caput, Monoallelically expressed gene related to p53 at 1p36, a region frequently deleted in neuroblastoma and other human cancers. Cell 90, 809-819 (1997).
9. P. M. Loughnan and P. N. McDougall, Does intramuscular vitamin K1 act as an unintended depot preparation? J. Paediatr. Child Health 32, 251-254 (1996).
10. Federal Register, New Drug and Biological Drug Products; Evidence Needed to Demonstrate Effectiveness of New Drugs When Human Efficacy Studies Are Not Ethical or Feasible, pp. 37988-37998. DHHS, FDA, Washington, DC, 2002.
11. R. R. Tice, The single cell gel/comet assay: a microgel electrophoretic technique for the detection of DNA damage and repair in individual cells. In Environmental Mutagenesis (V. S. Philips, Ed.), pp. 315-339. Bios Scientific Publishers, Oxford, 1996.
12. R. R. Tice, E. Agurell, D. Anderson, B. Burlinson, A. Hartmann, H. Kobayashi, Y. Miyamae, E. Rojas, J. C. Ryu and Y. F. Sasaki, Single cell gel/comet assay: guidelines for in vitro and in vivo genetic toxicology testing. Environ. Mol. Mutagen. 35, 206-221 (2000).
13. S. Brendler-Schwaab, A. Hartmann, S. Pfuhler and G. Speit, The in vivo comet assay: use and status in genotoxicity testing. Mutagenesis 20, 245-254 (2005).
14. A. Basu and S. Haldar, The relationship between Bcl2, Bax and p53: consequences for cell cycle progression and cell death. Mol. Hum. Reprod. 4, 1099-1109 (1998).
15. E. S. Child and D. J. Mann, The intricacies of p21 phosphorylation: protein/protein interactions, subcellular localization and stability. Cell Cycle 5, 1313-1319 (2006).
16. M. T. Hemann and S. W. Lowe, The p53-Bcl-2 connection. Cell Death Differ. 13, 1256-1259 (2006).
17. W. G. Kaelin, Jr., The p53 gene family. Oncogene 18, 7701-7705 (1999).
18. J. C. Reed, Proapoptotic multidomain Bcl-2/Bax-family proteins: mechanisms, physiological roles, and therapeutic opportunities. Cell Death Differ. 13, 1378-1386 (2006).
19. S. Strano and G. Blandino, p73-mediated chemosensitivity: a preferential target of oncogenic mutant p53. Cell Cycle 2, 348-349 (2003).
20. S. Zinkel, A. Gross and E. Yang, BCL2 family in DNA damage and cell cycle control. Cell Death Differ. 13, 1351-1359 (2006).
21. M. E. McCurrach, T. M. Connor, C. M. Knudson, S. J. Korsmeyer and S. W. Lowe, bax-deficiency promotes drug resistance and oncogenic transformation by attenuating p53-dependent apoptosis. Proc. Natl. Acad. Sci. USA 94, 2345-2349 (1997).
22. H. Xiang, Y. Kinoshita, C. M. Knudson, S. J. Korsmeyer, P. A. Schwartzkroin and R. S. Morrison, Bax involvement in p53-mediated neuronal cell death. J. Neurosci. 18, 1363-1373 (1998).
23. C. Yin, C. M. Knudson, S. J. Korsmeyer and T. Van Dyke, Bax suppresses tumorigenesis and stimulates apoptosis in vivo. Nature 385, 637-640 (1997).
24. M. Murphy, M. J. Mabruk, P. Lenane, A. Liew, P. McCann, A. Buckley, P. Billet, M. Leader, E. Kay and G. M. Murphy, The expression of p53, p21, Bax and induction of apoptosis in normal volunteers in response to different doses of ultraviolet radiation. Br. J. Dermatol. 147, 110-117 (2002).
25. M. Levrero, V. De Laurenzi, A. Costanzo, J. Gong, J. Y. Wang and G. Melino, The p53/p63/p73 family of transcription factors: overlapping and distinct functions. J. Cell Sci. 113, 1661-1670 (2000).
26. J. G. Gong, A. Costanzo, H. Q. Yang, G. Melino, W. G. Kaelin, Jr., M. Levrero and J. Y. Wang, The tyrosine kinase c-Abl regulates p73 in apoptotic response to cisplatin-induced DNA damage. Nature 399, 806-809 (1999).
27. C. E. Cole, H. T. Tran and P. M. Schlosser, Physiologically based pharmacokinetic modeling of benzene metabolism in mice through extrapolation from in vitro to in vivo. J. Toxicol. Environ. Health A 62, 439-465 (2001).
28. P. J. O'Brien, K. Chan and P. M. Silber, Human and animal hepatocytes in vitro with extrapolation in vivo. Chem. Biol. Interact. 150, 97-114 (2004).