Zhang B, Satoh M, Nishimura N, Suzuki J S, Sone H, Aoki Y, Tohyama C
Environmental Health Sciences Division, National Institute for Environmental Studies, Tsukuba, Ibaraki, Japan.
Cancer Res. 1998 Sep 15;58(18):4044-6.
To investigate a possible involvement of metallothionein (MT) in chemical carcinogenesis, MT-I and MT-II gene-deficient [MT (-/-)] transgenic mice and wild-type [MT (+/+)] control mice were topically applied at a single dose of 100, 250, 500, or 1000 microg of 7,12-dimethylbenz[a]anthracene (DMBA) on the dorsal skin and thereafter compared. After 14 weeks of DMBA treatment, the skin tumor occurred in MT (-/-) mice only and in a dose-dependent manner, whereas no change was observed in MT (+/+) mouse skin given the same DMBA treatment. The tumor cells showed proliferative activity, as shown by proliferative cell nuclear antigen staining. These results demonstrate that MT acts as an endogenous defensive factor against DMBA-induced skin tumorigenesis.
为研究金属硫蛋白（MT）在化学致癌过程中可能发挥的作用，将MT-I和MT-II基因缺陷型[MT（-/-）]转基因小鼠及野生型[MT（+/+）]对照小鼠的背部皮肤单次局部涂抹100、250、500或1000微克的7,12-二甲基苯并[a]蒽（DMBA），随后进行比较。DMBA处理14周后，皮肤肿瘤仅在MT（-/-）小鼠中出现，且呈剂量依赖性，而给予相同DMBA处理的MT（+/+）小鼠皮肤未观察到变化。肿瘤细胞显示出增殖活性，增殖细胞核抗原染色证明了这一点。这些结果表明，MT作为一种内源性防御因子，可抵御DMBA诱导的皮肤肿瘤发生。
