Protection against stress-mediated damage from ionizing radiation

Abstract

The use and screening of modulators of apoptosis is disclosed. The modulators may be, for example, modulator of NF-κB activity. The modulators may be used, for example, in the treatment of NF-κB-mediated diseases, conditions, and injuries.

1 . A method of protecting a mammal from a condition that triggers apoptosis comprising administering to a mammal in need thereof a composition comprising an agent that induces NF-kB. 
     
     
         2 . The method of  claim 1  wherein the agent is selected from the group consisting of flagellin and TGFβ. 
     
     
         3 . The method of  claim 2  wherein the agent is latent TGFβ. 
     
     
         4 . The method of  claim 1  wherein the condition is radiation exposure. 
     
     
         5 . The method of  claim 2  wherein the composition is administered in combination with a radioprotectant. 
     
     
         6 . The method of  claim 5  wherein the radioprotectant is an antioxidant. 
     
     
         7 . The method of  claim 6  wherein the antioxidant is selected from the group consisting of amifostine and vitamin E. 
     
     
         8 . The method of  claim 5  wherein the radioprotectant is a cytokine. 
     
     
         9 . The method of  claim 8 , wherein the cytokine is stem cell factor. 
     
     
         10 . The method of  claim 1  wherein the condition is a cancer treatment. 
     
     
         11 . The method of  claim 1  wherein the condition is a constitutively active NF-kB cancer. 
     
     
         12 . The method of  claim 10  wherein the cancer treatment is chemotherapy or radiation therapy. 
     
     
         13 . The method of  claim 10  wherein the composition is administered prior to, together with, or after the treatment. 
     
     
         14 . The method of  claim 1  wherein the condition is selected from the group consisting of cell aging, radiation, wounding, poisoning, infection and temperature shock. 
     
     
         15 . A method of screening for a modulator of apoptosis comprising:
 (a) adding a suspected modulator to a cell-based apoptosis system;   (b) separately adding a control to a cell-based apoptosis system; and   (c) comparing the level of apoptosis in steps (a) and (b);   
       wherein the suspected modulator is derived from a mammalian parasite. 
     
     
         16 . The method of  claim 15  wherein the modulator of apoptosis is a modulator of NF-kB, wherein the cell-based apoptosis system is a NF-kB-activated expression system, and wherein the level of apoptosis is the level of NF-kB-activated expression. 
     
     
         17 . The method of  claim 15  wherein the modulator of apoptosis is a modulator of TGFβ, wherein the cell-based apoptosis system is a TGFβ-activated expression system, and wherein the level of apoptosis is the level of TGFβ-activated expression. 
     
     
         18 . The method of  claim 15  wherein the modulator of apoptosis is a modulator of p53, wherein the cell-based apoptosis system is a p53-activated expression system, and wherein the level of apoptosis is the level of p53-activated expression. 
     
     
         19 . The method of  claim 15  wherein the parasite is a species selected from the group consisting of  Salmonella, Mycoplasma , and  Chlamydia.    
     
     
         20 . A modulator identified by the method of  claim 19 .