Postirradiation treatment with copper(II)2(3,5-diisopropylsalicylate)4 enhances radiation recovery and hemopoietic regeneration

Abstract

We have previously reported that copper(II)2(3,5-diisopropylsalicylate)4 (Cu-DIPS), administered 3 h before exposure to lethal irradiation, significantly increased the survival rate of mice. Agents that can improve recovery from irradiation are of particular importance for accidental radiation exposure if they are effective when given after exposure. In the present study, we showed that Cu-DIPS had radiation recovery activity when administered subsequent to radiation exposure. Mice were exposed to 800 cGy irradiation and 3 h later injected with vehicle or 20, 40, or 60 mumol/kg Cu-DIPS. The 30-day survival rate was significantly increased at all doses of Cu-DIPS tested. Survival increased from 47% for vehicle-treated mice to 78% (p less than 0.001) for mice treated with 40 mumol/kg. The recovery of hemopoietic activity was assessed in similarly treated mice 14 and 24 days after irradiation. The postirradiation Cu-DIPS treatment significantly increased spleen weights, bone marrow cellularity, and hemopoietic activity in the spleen and bone marrow compared to vehicle-treated controls. Enhanced recovery of hemopoietic activity included both committed progenitor granulocyte-macrophage colony-forming units (GM-CFU) and more primitive stem cells (endogenous spleen colony-forming units, CFU-Se). The number of CFU-Se at 14 days, the number of bone marrow GM-CFU at 24 days, and bone marrow cellularity at 24 days appear to be better predictors of survival rates than other parameters.