title: Elevation of metallothionein level in preneoplastic lesions during chemical hepatocarcinogenesis of the Fischer 344 rat.
abstract: Metallothionein (MT) is inducible by various stimuli such as metals and physiological stress. Although elevated MT expression in certain type of tumors has been reported, there are few data available on the roles of MT in tumor formation. In this study, we immunohistochemically examined MT expression in gluthathione S-transferase placental type p (GST-P)-positive preneoplastic liver lesions induced by a chemical carcinogen and further examined the relationship between MT expression and the proliferative activity of the preneoplastic cells, using bromodeoxyuridine (BrdU) labeling indices. Eleven male Fischer rats (F344/DuCrj, 9 weeks old) were subjected to the Solt-Farber protocol. Thereafter, the livers were removed, frozen and sectioned serially for immunohistochemical staining of MT and GST-P. Eight rats were given six injections of BrdU before sacrifice. In 92.8% of GST-P positive lesions, high MT staining intensity was demonstrated. On the other hand, there was no correlation between the intensity of MT staining and the BrdU labeling indices of the preneoplastic lesions. Our results indicate that MT is a useful positive marker for preneoplastic liver lesions, though the reason why MT is expressed in the preneoplastic and neoplastic lesions remains to be elucidated.
authors.affiliation: Hita Research Laboratories, Chemicals Inspection & Testing Institute, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Sawaki
authors.forename: K
authors.initials: K
authors.lastname: Enomoto
authors.forename: A
authors.initials: A
authors.lastname: Hattori
authors.forename: N
authors.initials: N
authors.lastname: Tsuzuki
authors.forename: N
authors.initials: N
authors.lastname: Sawada
authors.forename: M
authors.initials: M
authors.lastname: Mori
mesh_terms: D015073:2-Acetylaminofluorene; D000818:Animals; D004052:Diethylnitrosamine; D005982:Glutathione Transferase / Q000378:metabolism; D008113:Liver Neoplasms / Q000139:chemically induced / Q000378:metabolism*; D008114:Liver Neoplasms, Experimental / Q000139:chemically induced / Q000378:metabolism*; D008297:Male; D008668:Metallothionein / Q000378:metabolism*; D009153:Mutagens; D011230:Precancerous Conditions / Q000378:metabolism*; D051381:Rats; D011916:Rats, Inbred F344
chemical_list: D009153:Mutagens; D004052:Diethylnitrosamine; D008668:Metallothionein; D015073:2-Acetylaminofluorene; D005982:Glutathione Transferase