Administration of ON 01210.Na after exposure to ionizing radiation protects bone marrow cells by attenuating DNA damage response

Radiation Oncology

Volumn 7, Issue 1, 2012, Pages

  Suman, Shubhankar ^a   Maniar, Manoj ^b   Fornace Jr, Albert J ^a   Datta, Kamal ^a  

^a GEORGETOWN UNIVERSITY MEDICAL CENTER   (United States)

^b Onconova Therapeutics Inc   (United States)

Author keywords

Dna damage; Ex rad; Hematopoietic toxicity; On 01210.na; Radiation mitigation; Radiation toxicity

Indexed keywords

ATM PROTEIN; CESIUM 137; ON 01210NA; PROTEIN BAX; PROTEIN BCL 2; PROTEIN P53; RADIOPROTECTIVE AGENT; SULFONE DERIVATIVE; UNCLASSIFIED DRUG; (E) 4 CARBOXYSTYRYL 4 CHLOROBENZYLSULFONE, SODIUM SALT; (E)-4-CARBOXYSTYRYL-4-CHLOROBENZYLSULFONE, SODIUM SALT; GRANULOCYTE MACROPHAGE COLONY STIMULATING FACTOR; SULFONAMIDE;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; BONE MARROW CELL; BONE MARROW TOXICITY; CELL PROTECTION; COLONY FORMING UNIT GM; CONTROLLED STUDY; DNA DAMAGE; GAMMA RADIATION; IONIZING RADIATION; LEUKOCYTE COUNT; MALE; MOUSE; NICK END LABELING; NONHUMAN; RADIATION DOSE; RADIATION INJURY; RADIATION PROTECTION; THROMBOCYTE COUNT; WESTERN BLOTTING; ANIMAL; APOPTOSIS; BONE MARROW; C3H MOUSE; CELL CULTURE; CLONOGENIC ASSAY; DRUG EFFECT; RADIATION EXPOSURE;

ANIMALS; APOPTOSIS; BLOTTING, WESTERN; BONE MARROW; CELLS, CULTURED; COLONY-FORMING UNITS ASSAY; DNA DAMAGE; GAMMA RAYS; GRANULOCYTE-MACROPHAGE COLONY-STIMULATING FACTOR; MALE; MICE; MICE, INBRED C3H; RADIATION INJURIES; SULFONAMIDES;

EID: 84855992593     PISSN: None     EISSN: 1748717X     Source Type: Journal    
DOI: 10.1186/1748-717X-7-6     Document Type: Article

References (29)

1. Nenot JC. Radiation accidents over the last 60 years. J Radiol Prot 2009, 29:301-320. 10.1088/0952-4746/29/3/R01, 19690364.
2. Niazi AK, Niazi SK. Endocrine effects of Fukushima: Radiation-induced endocrinopathy. Indian J Endocrinol Metab 2011, 15:91-95. 10.4103/2230-8210.81936, 3125012, 21731864.
3. Citrin D, Cotrim AP, Hyodo F, Baum BJ, Krishna MC, Mitchell JB. Radioprotectors and mitigators of radiation-induced normal tissue injury. Oncologist 2010, 15:360-371. 10.1634/theoncologist.2009-S104, 3076305, 20413641.
4. Andrews GA. Radiation accidents and their management. Radiat Res Suppl 1967, 7:390-397.
5. Hall EJ, Giaccia AJ. 2006, Philadelphia: Lippincott Williams & Wilkins.
6. Moulder JE, Cohen EP. Future strategies for mitigation and treatment of chronic radiation-induced normal tissue injury. Semin Radiat Oncol 2007, 17:141-148. 10.1016/j.semradonc.2006.11.010, 17395044.
7. Fliedner TM, Friesecke I, Graessle D, Paulsen C, Weiss M. Hematopoietic cell renewal as the limiting factor in low-level radiation exposure: diagnostic implications and therapeutic options. Mil Med 2002, 167:46-48.
8. Williams JP, McBride WH. After the bomb drops: A new look at radiation-induced multiple organ dysfunction syndrome (MODS). Int J Radiat Biol 2011,
9. Maurya DK, Devasagayam TP, Nair CK. Some novel approaches for radioprotection and the beneficial effect of natural products. Indian J Exp Biol 2006, 44:93-114.
10. Nair CK, Parida DK, Nomura T. Radioprotectors in radiotherapy. J Radiat Res (Tokyo) 2001, 42:21-37.
11. Zhou BB, Elledge SJ. The DNA damage response: putting checkpoints in perspective. Nature 2000, 408:433-439. 10.1038/35044005, 11100718.
12. Tanaka T, Huang X, Jorgensen E, Gietl D, Traganos F, Darzynkiewicz Z, Albino AP. ATM activation accompanies histone H2AX phosphorylation in A549 cells upon exposure to tobacco smoke. BMC Cell Biol 2007, 8:26. 10.1186/1471-2121-8-26, 1919366, 17594478.
13. Maya R, Balass M, Kim ST, Shkedy D, Leal JF, Shifman O, Moas M, Buschmann T, Ronai Z, Shiloh Y, Kastan MB, Katzir E, Oren M. ATM-dependent phosphorylation of Mdm2 on serine 395: role in p53 activation by DNA damage. Genes Dev 2001, 15:1067-1077. 10.1101/gad.886901, 312683, 11331603.
14. Bache M, Pigorsch S, Dunst J, Wurl P, Meye A, Bartel F, Schmidt H, Rath FW, Taubert H. Loss of G2/M arrest correlates with radiosensitization in two human sarcoma cell lines with mutant p53. Int J Cancer 2001, 96:110-117. 10.1002/ijc.1002, 11291094.
15. Mazzatti DJ, Lee YJ, Helt CE, O'Reilly MA. p53 modulates radiation sensitivity independent of p21 transcriptional activation. Am J Clin Oncol 2005, 28:43-50. 10.1097/01.coc.0000139484.51715.5a, 15685034.
16. Zhan Q, Kontny U, Iglesias M, Alamo IJ, Yu K, Hollander MC, Woodworth CD, Fornace AJJ. Inhibitory effect of Bcl-2 on p53-mediated transactivation following genotoxic stress. Oncogene 1999, 18:297-304. 10.1038/sj.onc.1202310, 9927186.
17. Dlugosz PJ, Billen LP, Annis MG, Zhu W, Zhang Z, Lin J, Leber B, Andrews DW. Bcl-2 changes conformation to inhibit Bax oligomerization. EMBO J 2006, 25:2287-2296. 10.1038/sj.emboj.7601126, 1478188, 16642033.
18. Ghosh SP, Perkins MW, Hieber K, Kulkarni S, Kao TC, Reddy EP, Reddy MV, Maniar M, Seed T, Kumar KS. Radiation protection by a new chemical entity Ex-Rad: efficacy and mechanisms. Radiat Res 2009, 171:173-179. 10.1667/RR1367.1, 19267542.
19. Chun AW, Cosenza SC, Taft DR, Maniar M. Preclinical pharmacokinetics and in vitro activity of ON 01910.Na, a novel anti-cancer agent. Cancer Chemother Pharmacol 2009, 65:177-186. 10.1007/s00280-009-1022-9, 19466411.
20. Chun AW, Freshwater RE, Taft DR, Gillum AM, Maniar M. Effects of formulation and route of administration on the systemic availability of Ex-RAD((R)), a new radioprotectant, in preclinical species. Biopharm Drug Dispos 2011, 32:99-111. 10.1002/bdd.741, 21341279.
21. Singh VK, Parekh VI, Brown DS, Kao TC, Mog SR. Tocopherol succinate: modulation of antioxidant enzymes and hematopoietic recovery. Int J Radiat Oncol Biol Phys 2011, 79:571-578. 10.1016/j.ijrobp.2010.08.019, 20950962.
22. Western blot analysis protocol. , http://rsb.info.nih.gov/ij/docs/menus/analyze.html#gels
23. Pellmar TC, Rockwell S. Priority list of research areas for radiological nuclear threat countermeasures. Radiat Res 2005, 163:115-123. 10.1667/RR3283, 15606315.
24. Yang FT, Lord BI, Hendry JH. Gamma irradiation of the fetus damages the developing hemopoietic microenvironment rather than the hemopoietic progenitor cells. Radiat Res 1995, 141:309-313. 10.2307/3579008, 7871158.
25. Gridley DS, Pecaut MJ. Whole-body irradiation and long-term modification of bone marrow-derived cell populations by low- and high-LET radiation. In Vivo 2006, 20:781-789.
26. Gridley DS, Pecaut MJ, Miller GM, Moyers MF, Nelson GA. Dose and dose rate effects of whole-body gamma-irradiation: II. Hematological variables and cytokines. In Vivo 2001, 15:209-216.
27. Weiss JF, Landauer MR. History and development of radiation-protective agents. Int J Radiat Biol 2009, 85:539-573. 10.1080/09553000902985144, 19557599.
28. Domen J, Gandy KL, Weissman IL. Systemic overexpression of BCL-2 in the hematopoietic system protects transgenic mice from the consequences of lethal irradiation. Blood 1998, 91:2272-2282.
29. Xiang J, Chao DT, Korsmeyer SJ. BAX-induced cell death may not require interleukin 1 beta-converting enzyme-like proteases. Proc Natl Acad Sci USA 1996, 93:14559-14563. 10.1073/pnas.93.25.14559, 26172, 8962091.