Vol. 286, Issue 3, 1427-1430, September 1998

Protective Effect of Bismuth Nitrate Against Injury to the Bone Marrow by -Irradiation in Mice: Possible Involvement of Induction of Metallothionein Synthesis¹

Nobuhiko Miura, Masahiko Satoh, Nobumasa Imura and Akira Naganuma

Department of Molecular and Biochemical Toxicology, Faculty of Pharmaceutical Sciences, Tohoku University, Aoba-ku, Sendai 980-8578, Japan (N.M., A.N.); Department of Public Health and Molecular Toxicology, School of Pharmaceutical Sciences, Kitasato University, Minato-Ku, Tokyo 108-8641, Japan (N.I.); and Environmental Health Sciences Division, National Institute for Environmental Studies Tsakuba, Ibavaki, 305-0053, Japan (M.S.)

The effects of bismuth nitrate (BN) on the lethal effect of and injury to bone marrow by -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 -irradiation without treatment with BN died within 30 days, but the lethal effect of -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 -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 -irradiation by inducing the synthesis of metallothionein in the bone marrow. Metallothionein might play an important role in determining the sensitivity of animals to -irradiation.