Protective role of metallothionein in bone marrow injury caused by X-irradiation.
In order to elucidate the role of metallothionein (MT) in preventing the adverse effects of X-ray irradiation, we examined the susceptibility of MT-I/II null mice to bone marrow injury caused by X-irradiation and effects of pretreatment with MT-inducing metals on X-ray injury. Eight-week-old male mice were exposed to a single bout of whole-body X-irradiation at a dose between 0.1 and 6.0 Gy. The numbers of leukocytes, reticulocytes with micronuclei (MNRET) in the blood, and polychromatic erythrocytes with micronuclei (MNPCE) in the bone marrow were determined 24 hr after X-irradiation. X-irradiation significantly decreased the total number of leukocytes in MT-I/II null mice and wild-type mice in a dose-dependent manner, but the total number of leukocytes was significantly lower in MT-I/II null mice than in wild-type mice at a low dose of irradiation, between 0.1 and 1.0 Gy. X-irradiation (0.1 and 0.5 Gy) significantly increased the appearance of MNRET and MNPCE in both strains, but the increase was greater in the MT-I/II null mice than in the wild-type mice. Additional groups of mice were pre-administered bismuth nitrate or zinc sulfate to induce MT in the bone marrow cells prior to X-irradiation; the X-ray injury was prevented by such treatments in wild-type mice only. Thus, the present results suggest that MT plays a protective role against a low dose of X-ray injury.
Shibuya
Kiyoshi
K
Laboratory of Molecular and Biochemical Toxicology, Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai, Japan.
Suzuki
Junko S
JS
Kito
Hideaki
H
Naganuma
Akira
A
Tohyama
Chiharu
C
Satoh
Masahiko
M
D000818:Animals; D001729:Bismuth / Q000633:toxicity; D001853:Bone Marrow / Q000528:radiation effects*; D004307:Dose-Response Relationship, Radiation; D004912:Erythrocytes / Q000528:radiation effects; D007962:Leukocytes / Q000528:radiation effects; D008297:Male; D008668:Metallothionein / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D048629:Micronuclei, Chromosome-Defective / Q000528:radiation effects; D009566:Nitrates / Q000633:toxicity; D012156:Reticulocytes / Q000166:cytology; D014916:Whole-Body Irradiation / Q000009:adverse effects*; D014965:X-Rays / Q000009:adverse effects*; D019287:Zinc Sulfate / Q000633:toxicity
D009566:Nitrates; C065545:bismuth nitrate; D019287:Zinc Sulfate; D008668:Metallothionein; D001729:Bismuth