title: Metallothionein deficiency promotes mouse skin carcinogenesis induced by 7,12-dimethylbenz[a]anthracene.
abstract: 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.
authors.affiliation: Environmental Health Sciences Division, National Institute for Environmental Studies, Tsukuba, Ibaraki, Japan.
authors.forename: B
authors.initials: B
authors.lastname: Zhang
authors.forename: M
authors.initials: M
authors.lastname: Satoh
authors.forename: N
authors.initials: N
authors.lastname: Nishimura
authors.forename: J S
authors.initials: JS
authors.lastname: Suzuki
authors.forename: H
authors.initials: H
authors.lastname: Sone
authors.forename: Y
authors.initials: Y
authors.lastname: Aoki
authors.forename: C
authors.initials: C
authors.lastname: Tohyama
mesh_terms: D015127:9,10-Dimethyl-1,2-benzanthracene; D000818:Animals; D002273:Carcinogens; D004305:Dose-Response Relationship, Drug; D008668:Metallothionein / Q000172:deficiency* / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D009374:Neoplasms, Experimental / Q000139:chemically induced / Q000473:pathology; D018809:Proliferating Cell Nuclear Antigen / Q000032:analysis; D012878:Skin Neoplasms / Q000139:chemically induced* / Q000473:pathology
chemical_list: D002273:Carcinogens; D018809:Proliferating Cell Nuclear Antigen; D015127:9,10-Dimethyl-1,2-benzanthracene; D008668:Metallothionein