Further studies on selective radioprotection by organic zinc salts and synergism of zinc aspartate with WR 2721.
The organic zinc salts zinc aspartate, zinc histidine, zinc orotate and zinc acetate reduced the fall of the haematocrit, thrombocytes, erythrocytes and leucocytes in irradiated mice. In general, zinc aspartate was more effective than the other organic zinc salts. Protection of the haematocrit and thrombocytes by small doses of the aminothiol radioprotector WR 2721 was markedly improved by the concomitant administration of small doses of zinc aspartate. Zinc aspartate was the only one of the four tested organic zinc salts that did not inhibit in any instance the regression induced by radiotherapy of human tumours grown as xenografts in immunosuppressed mice. This also applied to the combination of zinc aspartate with WR 2721. In an experiment performed to determine the toxicity of the combined regimen, a dose of zinc aspartate which afforded synergistic haematological protection did not enhance the toxicity of WR 2721. The synergism of zinc aspartate with WR 2721 and the differential radioprotection of the combined protocol may make it possible in clinical cancer radiotherapy to obtain selective radioprotection at a lower toxicity giving an improved therapeutic ratio compared with WR 2721 alone.
Floersheim
G L
GL
Department of Research, Kantonsspital, Basel, Switzerland.
Bieri
A
A
D000085:Acetates / Q000494:pharmacology; D019342:Acetic Acid; D004999:Amifostine / Q000494:pharmacology*; D000818:Animals; D001772:Blood Cell Count / Q000187:drug effects / Q000528:radiation effects; D004357:Drug Synergism; D005260:Female; D006639:Histidine / Q000494:pharmacology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D009374:Neoplasms, Experimental / Q000097:blood / Q000532:radiotherapy; D009381:Neoplasms, Radiation-Induced / Q000532:radiotherapy; D009942:Organometallic Compounds / Q000494:pharmacology; D009946:Organothiophosphorus Compounds / Q000494:pharmacology*; D009963:Orotic Acid; D011837:Radiation-Protective Agents / Q000494:pharmacology*; D015032:Zinc / Q000494:pharmacology*
D000085:Acetates; D009942:Organometallic Compounds; D009946:Organothiophosphorus Compounds; D011837:Radiation-Protective Agents; C052388:zinc-histidine complex; D006639:Histidine; D009963:Orotic Acid; D015032:Zinc; D004999:Amifostine; D019342:Acetic Acid