Radiation-induced lymphoid tumors and radiation lethality are inhibited by combined treatment with small doses of zinc aspartate and WR 2721.
Combined small doses of zinc aspartate and WR 2721 provided additive protection against radiation lethality in mice. Survival obtained with a small dose of WR 2721 which was ineffective alone could be enhanced to 83% by combining the drug with zinc aspartate, which on its own also displayed no effect. The survival of 25% provided by a higher dose of WR 2721 was increased significantly by adding zinc aspartate. Additivity was also tested in a model of radiation carcinogenesis. For this purpose, lethality and occurrence of lymphoid tumors induced by fractionated total-body irradiation were studied in C57B1/6 mice treated with zinc aspartate and WR 2721. In order to reveal additive effects, both agents were used at sub-optimal dosages. In mice subjected to 5 daily exposures of 1.9 Gy, the combination of zinc aspartate and WR 2721 was effective and enhanced the survival to 83% as compared with 25% afforded by WR 2721 alone (p < 0.005). Similarly, histological assessment of organ involvement with lymphoma revealed that zinc aspartate and WR 2721 alone did not bring about a significant reduction of lymphoma incidence. On the other hand, the combined agents diminished organ involvement with lymphoma to 9.1% as against 90% in the controls (p < 0.0005) and 62.5% with WR 2721 alone (p < 0.025). Thus, combined treatment with zinc aspartate and WR 2721 also inhibited radiation-induced lymphoid tumors.
Floersheim
G L
GL
Department of Research, Kantonsspital Basel, Switzerland.
Christ
A
A
Koenig
R
R
Racine
C
C
Gudat
F
F
D004999:Amifostine / Q000008:administration & dosage*; D000818:Animals; D001224:Aspartic Acid / Q000008:administration & dosage*; D004359:Drug Therapy, Combination; D005260:Female; D008223:Lymphoma / Q000517:prevention & control*; D051379:Mice; D008809:Mice, Inbred C3H; D009381:Neoplasms, Radiation-Induced / Q000473:pathology / Q000517:prevention & control*; D011837:Radiation-Protective Agents / Q000627:therapeutic use*; D015032:Zinc / Q000008:administration & dosage*
D011837:Radiation-Protective Agents; D001224:Aspartic Acid; D015032:Zinc; D004999:Amifostine