title: Significance of overexpression of metallothionein in mouse urinary bladder focal lesions induced by treatment with N-butyl-N-(4-hydroxybutyl)-nitrosamine.
abstract: Metallothionein (MT) is expressed in various types of human tumors, including transitional cell carcinomas of the urinary bladder, but its biological significance remains unclear. In the present study, the role of MT in urinary bladder carcinogenesis induced by N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN) treatment was investigated using C57BL/6 mice. One hundred 5-week-old male C57BL/6 mice were divided into two groups, which were given drinking water with or without 0.05% BBN throughout the experimental period. Subgroups of ten animals from each group were sacrificed at weeks 5, 10, 15, 20 and 25, and urinary bladder samples were examined immunohistochemically for MT, proliferating cell nuclear antigen (PCNA) and apoptosis. MT was found to be abundant in normal-looking mucosa, but decreased with progression from precancerous lesions to invasive carcinoma in the urinary bladder obtained from BBN-treated mice. Lesions could be divided into MT-positive and negative. There was a tendency for greater MT expression in PCNA-positive lesions, while apoptosis was rather associated with MT-negativity. These data suggest that the overexpression of MT may play a role in mouse urinary bladder carcinogenesis.
authors.affiliation: Department of Pathology, Osaka City University Medical School, 1-4-3 Asahi-machi, Abeno-ku, Osaka 545-8585.
authors.forename: Makoto
authors.initials: M
authors.lastname: Mitsuhashi
authors.forename: Hideki
authors.initials: H
authors.lastname: Wanibuchi
authors.forename: Keiichirou
authors.initials: K
authors.lastname: Morimura
authors.forename: Ken'ichiro
authors.initials: K
authors.lastname: Doi
authors.forename: Min
authors.initials: M
authors.lastname: Wei
authors.forename: Seiji
authors.initials: S
authors.lastname: Wada
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Nakatani
authors.forename: Shoji
authors.initials: S
authors.lastname: Fukushima
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology; D002085:Butylhydroxybutylnitrosamine / Q000633:toxicity*; D002273:Carcinogens / Q000633:toxicity*; D007150:Immunohistochemistry; D008297:Male; D008668:Metallothionein / Q000096:biosynthesis*; D051379:Mice; D008810:Mice, Inbred C57BL; D011230:Precancerous Conditions / Q000378:metabolism* / Q000473:pathology; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D001743:Urinary Bladder / Q000378:metabolism / Q000473:pathology; D001749:Urinary Bladder Neoplasms / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology
chemical_list: D002273:Carcinogens; D018809:Proliferating Cell Nuclear Antigen; D002085:Butylhydroxybutylnitrosamine; D008668:Metallothionein