Radioprotective effects of the immunomodulator AS101.
Ammonium trichloro(dioxyethylene-O-O')tellurate (AS101) is a new synthetic compound previously described by us as having immunomodulating properties and minimal toxicity. Clinical trials are currently in progress with AS101 on AIDS and cancer patients. We found that AS101 was capable of inducing spleen cells and peritoneal exudate cells to secrete high quantities of CSF and IL-1. Because IL-1 has been previously described as a radioprotector and CSF may induce in vivo the proliferation of hemopoietic cells, we designed the present study in order to evaluate the effects of prolonged in vivo injections of AS101 on protection against lethal doses of irradiation, on the recovery pattern of precursor cells, and on the functioning of bone marrow (BM) and spleen cells of mice undergoing sublethal doses of treatment. We demonstrate that pretreatment with AS101 protects mice from lethal effects of ionizing radiation. AS101 was also found to significantly increase the number of BM and spleen cells, the absolute number of granulocyte macrophage-CFU and the secretion of CSF by BM cells. All were tested 9 days after sublethal dose of irradiation was administered. AS101 was found to have all of these radioprotective effects only when administered to mice before irradiation treatment. Moreover, the compound was found to enhance the proportion of CFU-S that enters the S phase of the cell cycle. These findings indicate that AS101 may be a promising agent to be used in reducing the time needed for reconstitution of hemopoietic cells after irradiation treatment.
Kalechman
Y
Y
Department of Life Sciences, Bar Ilan University, Ramat Gan, Israel.
Albeck
M
M
Oron
M
M
Sobelman
D
D
Gurwith
M
M
Seghal
S N
SN
Sredni
B
B
D000276:Adjuvants, Immunologic; D000818:Animals; D001854:Bone Marrow Cells; D002478:Cells, Cultured; D003115:Colony-Stimulating Factors / Q000378:metabolism; D005030:Ethylenes / Q000494:pharmacology*; D006410:Hematopoiesis; D007375:Interleukin-1 / Q000096:biosynthesis; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D011833:Radiation Injuries, Experimental / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control; D011837:Radiation-Protective Agents; D051381:Rats; D013154:Spleen / Q000166:cytology
D000276:Adjuvants, Immunologic; D003115:Colony-Stimulating Factors; D005030:Ethylenes; D007375:Interleukin-1; D011837:Radiation-Protective Agents; C054105:ammonium trichloro(dioxoethylene-O,O'-)tellurate