title: Radiation-induced lymphoid tumors and radiation lethality are inhibited by combined treatment with small doses of zinc aspartate and WR 2721.
abstract: 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.
authors.affiliation: Department of Research, Kantonsspital Basel, Switzerland.
authors.forename: G L
authors.initials: GL
authors.lastname: Floersheim
authors.forename: A
authors.initials: A
authors.lastname: Christ
authors.forename: R
authors.initials: R
authors.lastname: Koenig
authors.forename: C
authors.initials: C
authors.lastname: Racine
authors.forename: F
authors.initials: F
authors.lastname: Gudat
mesh_terms: 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*
chemical_list: D011837:Radiation-Protective Agents; D001224:Aspartic Acid; D015032:Zinc; D004999:Amifostine