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学科主题: 公共卫生
题名:
Metallothionein deficiency enhances skin carcinogenesis induced by 7,12-dimethylbenz[a]anthracene and 12-O-tetradecanoylphorbol-13-acetate in metallothionein-null mice
作者: Suzuki, JS; Nishimura, N; Zhang, BX; Nakatsuru, Y; Kobayashi, S; Satoh, M; Tohyama, C
刊名: CARCINOGENESIS
发表日期: 2003-06-01
DOI: 10.1093/carcin/bgg052
卷: 24, 期:6, 页:1123-1132
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Oncology
研究领域[WOS]: Oncology
关键词[WOS]: POLYCYCLIC AROMATIC-HYDROCARBONS ; GTPASE ACTIVATING PROTEIN ; EPOXIDE-DNA-BINDING ; TREATED MOUSE SKIN ; H-RAS GENE ; METABOLIC-ACTIVATION ; OXIDATIVE STRESS ; RADICAL CATIONS ; PROTECTIVE ROLE ; EXPRESSION
英文摘要:

To clarify the physiological role(s) of metallothionein (MT) in carcinogenesis, we studied the susceptibility of MT-null mice to chemically mediated carcinogenesis in the 7,12-dimethylbenz[a]anthracene (DMBA)/12-O-tetradecanoylphorbol-13-acetate (TPA)-induced two-stage carcinogenesis model. The MT-null mice were subjected to a single topical application of DMBA (50 or 100 mug/mouse) and, 1 week later, to promotion with TPA (10 mug/mouse) twice a week for 20 weeks. At week 21, nearly all of the MT-null mice developed tumors in the skin, in contrast to only 10-40% of wild-type mice. No tumors were observed in MT-null or wild-type mice that were administered TPA alone. By using the PCR-restriction fragment length polymorphism and PCR-single strand conformation polymorphism methods, we found a transversion of A(182) to T in codon 61 of c-Ha-ras in the papilloma tissue of MT-null mice and wild-type mice but failed to find any mutations in the c-Ki-ras and c-N-ras genes. In two-stage skin carcinogenesis induction by DMBA/TPA, p53 and p21(WAF1/Cip1) expression levels were found to be increased in MT-null mice compared with wild-type mice. As to an earlier change at the promotion stage triggered by TPA application, MT-null mice were found to have both hyperplasia of the epithelium and a marked degree of inflammation in the basal layer, indicating that the induced as well as endogenous MT acted as a protective factor against tumorigenesis. In conclusion, the present study has demonstrated that MT has antitumorigenic potential in both the initiation and promotion stages of the two-stage chemical skin carcinogenesis model.

语种: 英语
WOS记录号: WOS:000183836800015
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/67361
Appears in Collections:北京大学公共卫生学院_毒理学系_期刊论文

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作者单位: 1.Natl Inst Environm Studies, Environm Hlth Sci Div, Tsukuba, Ibaraki 3058506, Japan
2.Beijing Univ, Sch Publ Hlth, Dept Toxicol, Beijing 100083, Peoples R China
3.Univ Tokyo, Grad Sch Med, Dept Mol Pathol, Tokyo 1130033, Japan
4.Kyoritsu Coll Pharmaceut Sci, Dept Biol, Tokyo 1058512, Japan
5.Gifu Pharmaceut Univ, Dept Hyg, Gifu 5028585, Japan

Recommended Citation:
Suzuki, JS,Nishimura, N,Zhang, BX,et al. Metallothionein deficiency enhances skin carcinogenesis induced by 7,12-dimethylbenz[a]anthracene and 12-O-tetradecanoylphorbol-13-acetate in metallothionein-null mice[J]. CARCINOGENESIS,2003,24(6):1123-1132.
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