PROTECTIVE EFFECT OF BISMUTH NITRATE AGAINST INJURY TO THE BONE-MARROW BY GAMMA-IRRADIATION IN MICE - POSSIBLE INVOLVEMENT OF INDUCTION OF METALLOTHIONEIN SYNTHESIS

The effects of bismuth nitrate (BN) on the lethal effect of and injury to bone marrow by gamma-irradiation were examined. Mice were given da ily s.c. injections of BN for 2 days and were exposed to whole-body ir radiation (Cs-137; 8 grays) 24 hr after the second injection of BN. Al l mice exposed to gamma-irradiation without treatment with BN died wit hin 30 days, but the lethal effect of gamma-irradiation was markedly r educed in mice given BN before irradiation. Irradiation (3 grays) sign ificantly reduced the total number of leukocytes 1 day after irradiati on but the number of leukocytes subsequently increased in both nontrea ted and BN-treated irradiated mice. However, the rate of recovery of t he total number of leukocytes, as monitored from 5 days after irradiat ion, was significantly higher in BN-treated mice than in the nontreate d mice. Reductions in the viability of hematopoietic stem cells (deter mined by monitoring the number of colony-forming units in the spleen) that were induced by gamma-irradiation (3 grays) were considerably dim inished by the treatment of mice with BN before irradiation. BN signif icantly increased the concentration of metallothionein in the bone mar row cells of mice, but levels of other cellular antioxidants, such as catalase, superoxide dismutase, glutathione-S-transferase, glutathione peroxidase and glutathione, were unchanged. These results suggest tha t BN protects bone marrow cells against the toxic effects of gamma-irr adiation by inducing the synthesis of metallothionein in the bone marr ow. Metallothionein might play an important role in determining the se nsitivity of animals to gamma-irradiation.