Elevation of metallothionein level in preneoplastic lesions during chemical hepatocarcinogenesis of the Fischer 344 rat

Metallothionein (MT) is inducible by various stimuli such as metals and phy siological stress. Although elevated MT expression in certain type of tumor s has been reported, there are few data available on the roles of MT in tum or formation. In this study, we immunohistochemically examined MT expressio n in gluthathione S-transferase placental type p (GST-P)-positive preneopla stic liver lesions induced by a chemical carcinogen and further examined th e relationship between MT expression and the proliferative activity of the preneoplastic cells, using bromodeoxyuridine (BrdU) labeling indices, Eleve n male Fischer rats (F344/DuCrj, 9 weeks old) were subjected to the Solt-Fa rber protocol, Thereafter, the livers were removed, frozen and sectioned se rially for immunohistochemical staining of MT and GST-P. Eight rats were gi ven six injections of BrdU before sacrifice. In 92.8% of GST-P positive les ions, high MT staining intensity was demonstrated. On the other hand, there was no correlation between the intensity of MT staining and the BrdU label ing 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. (C) 1999 Elsevier Science Ireland Ltd. All rights reserved.