Radioprotective properties of detoxified lipid A from Salmonella minnesota R595.
In the past, the toxicity of bacterial lipopolysaccharide (LPS) or its principal bioactive component, lipid A, has detracted from their potential use as radioprotectants. Recently, a relatively nontoxic monophosphoryl Lipid A (LAM) that retains many of the immunobiologic properties of LPS has been isolated from a polysaccharide deficient Re mutant strain of Salmonella minnesota (R595). The ability of the native endotoxic glycolipid (GL) from S. minnesota (R595) as well as diphosphoryl lipid A (LAD) and nontoxic monophosphoryl lipid A (LAM) derived from GL to protect LPS responsive (CD2F1 or C3H/HeN) and nonresponsive (C3H/HeJ) mice from 60Co gamma irradiation has been studied. Administration of GL, LAD, or LAM to CD2F1 or C3H/HeN mice (400 micrograms/kg) 24 h prior to exposure provided significant radioprotection. No protection was afforded to C3H/HeJ mice. Experiments were also conducted to determine the relative abilities of GL, LAD, and LAM to stimulate hematopoiesis as reflected by the endogenous spleen colony (E-CFU) assay. Protection was not correlated with the ability of these substances to increase E-CFUs or to induce colony-stimulating activity (CSA).
D000818:Animals; D003037:Cobalt Radioisotopes; D003115:Colony-Stimulating Factors / Q000096:biosynthesis; D004731:Endotoxins / Q000627:therapeutic use; D005260:Female; D005720:Gamma Rays; D006017:Glycolipids / Q000627:therapeutic use; D008050:Lipid A / Q000031:analogs & derivatives / Q000627:therapeutic use*; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D011833:Radiation Injuries, Experimental / Q000517:prevention & control*; D011837:Radiation-Protective Agents / Q000627:therapeutic use*; D012475:Salmonella / Q000032:analysis
D003037:Cobalt Radioisotopes; D003115:Colony-Stimulating Factors; D004731:Endotoxins; D006017:Glycolipids; D008050:Lipid A; D011837:Radiation-Protective Agents; C049596:diphosphoryl lipid A; C048436:monophosphoryl lipid A