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 daily s.c. injections of BN for 2 days and were exposed to whole-body irradiation (137Cs; 8 grays) 24 hr after the second injection of BN. All mice exposed to gamma-irradiation without treatment with BN died within 30 days, but the lethal effect of gamma-irradiation was markedly reduced in mice given BN before irradiation. Irradiation (3 grays) significantly reduced the total number of leukocytes 1 day after irradiation but the number of leukocytes subsequently increased in both nontreated and BN-treated irradiated mice. However, the rate of recovery of the total number of leukocytes, as monitored from 5 days after irradiation, was significantly higher in BN-treated mice than in the nontreated mice. Reductions in the viability of hematopoietic stem cells (determined by monitoring the number of colony-forming units in the spleen) that were induced by gamma-irradiation (3 grays) were considerably diminished by the treatment of mice with BN before irradiation. BN significantly increased the concentration of metallothionein in the bone marrow 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 that BN protects bone marrow cells against the toxic effects of gamma-irradiation by inducing the synthesis of metallothionein in the bone marrow. Metallothionein might play an important role in determining the sensitivity of animals to gamma-irradiation.