Role of metallothionein as a protective factor against radiation carcinogenesis.
In order to elucidate the involvement of metallothionein (MT) in radiation carcinogenesis, we examined the susceptibility of MT-I/II null mice to carcinogenesis and oxidative DNA damage resulting from X-irradiation. Eight-week-old female MT-I/II null mice and wild-type mice were exposed to whole-body X-irradiation at doses of 1.0, 1.5 or 2.0 Gy once a week for 6 weeks. Incidence of thymic lymphoma was determined at 24 weeks after the first exposure to X-irradiation. The frequency of thymic lymphomas induced by X-irradiation (at 1.5 and 2.0 Gy) was significantly higher in MT-I/II null mice than in wild-type mice. In addition, although the levels of 8-hydroxy-2'-deoxyguanosine (8-OHdG) were increased in the serum and urine of both strains of mice 24 hr after exposure to a single bout of whole body X-irradiation, these increases were significantly greater in the MT-I/II null mice than in the wild-type mice. Thus, the present results suggest that MT plays a protective role against carcinogenesis and oxidative DNA damage caused by X-irradiation.
Shibuya
Kiyoshi
K
Nishimura
Noriko
N
Suzuki
Junko S
JS
Tohyama
Chiharu
C
Naganuma
Akira
A
Satoh
Masahiko
M
D000080242:8-Hydroxy-2'-Deoxyguanosine; D000818:Animals; D004249:DNA Damage; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000097:blood / Q000652:urine; D005260:Female; D008223:Lymphoma / Q000209:etiology / Q000235:genetics / Q000378:metabolism*; D008668:Metallothionein / Q000235:genetics / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D009381:Neoplasms, Radiation-Induced / Q000209:etiology / Q000235:genetics / Q000378:metabolism*; D013953:Thymus Neoplasms / Q000209:etiology / Q000235:genetics / Q000378:metabolism*; D014965:X-Rays
D000080242:8-Hydroxy-2'-Deoxyguanosine; D008668:Metallothionein; D003849:Deoxyguanosine