Shibuya Kiyoshi, Nishimura Noriko, Suzuki Junko S, Tohyama Chiharu, Naganuma Akira, Satoh Masahiko
J Toxicol Sci. 2008 Dec;33(5):651-5. doi: 10.2131/jts.33.651.
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.
为了阐明金属硫蛋白(MT)在辐射致癌中的作用,我们研究了MT-I/II基因敲除小鼠对X射线照射诱导的致癌作用和氧化性DNA损伤的易感性。8周龄雌性MT-I/II基因敲除小鼠和野生型小鼠每周接受一次剂量为1.0、1.5或2.0 Gy的全身X射线照射,共照射6周。在首次接受X射线照射后24周时测定胸腺淋巴瘤的发生率。X射线照射(1.5和2.0 Gy)诱导的MT-I/II基因敲除小鼠胸腺淋巴瘤的发生率显著高于野生型小鼠。此外,尽管在单次全身X射线照射24小时后,两种品系小鼠的血清和尿液中8-羟基-2'-脱氧鸟苷(8-OHdG)水平均升高,但MT-I/II基因敲除小鼠的升高幅度显著大于野生型小鼠。因此,目前的结果表明MT对X射线照射引起的致癌作用和氧化性DNA损伤具有保护作用。