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Metallothionein Deficiency Promotes Mouse Skin Carcinogenesis Induced by 7,12-Dimethylbenz[a]anthracene¹

Environmental Health Sciences Division, National Institute for Environmental Studies, Tsukuba, Ibaraki 305-0053, Japan [B. Z., M. S., N. N., J. S. S., H. S., Y. A., C. T.], and Department of Toxicology, Institute of Environmental Medicine, School of Public Health, Beijing Medical University, Beijing 100083, China [B. Z.]

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 µg 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.

¹ This work was supported in part by Eco-Frontier Fellowship of Environmental Agency (to B. Z.).

² To whom requests for reprints should be addressed.

Received 6/18/98. Accepted 7/28/98.

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