Summanr The chemoprotective effect of vanadium, a dietary micronutnrent. against chemically induced hepatocarcinogenesis in rats was investigated. Initiation was performed by a single intraperitoneal injection of diethylnitrosamine (DENA; 200 mg kg-') followed by promotion with phenobarbital (0.05 %) in the diet.Supplementary vanadium (0.5 p.p.m.) in the drinking water was provided ad libitum throughout the experiment. before the initiation or during the promotion period. At the end of the study (20 weeks Sabbioni et al., 1991: French and Jones, 1993Bishayee and Chatterjee, 1994). Scanning of pertinent literature reveals that many naturally occurring products and trace elements present in various foods may prevent, halt or reverse the neoplastic process (Wattenberg, 1985;Greenwald et al., 1987). Vanadium, an endogenous constituent of all or most mammalian tissues, is believed to have a regulatory role in biological systems (Crans et al., 1989;Gullapalli et al., 1989). Studies carried out in the last decade suggest that this transition metal could be considered a representative of a new class of non-platinum group metal anti-tumour agents (Kopf-Maier, 1987). Although Kingsnorth et al. (1986) observed that vanadate supplementation in diet or drinking water had little or no effect on 1,2-dimethylhydrazine-induced colon cancer in mice. Djordjevic and Wampler (1985) reported a significant antitumour activity of vanadium complexes against L1210 murine leukaemia. Vanadium at > 10-6M inhibited in vitro tumour colony formation, as was evident from a human tumour cloning assay (Hanauske et al., 1987). Dietary vanadium was found to block the induction of murine mammary carcinogenesis by 1-methyl-l-nitrosourea (Thompson et al., 1984). Previously, we have documented a significant protective response of vanadium (Sardar et al.. 1993) Chatterjee, 1995). The observed chemoprotective action of vanadium was found to be mediated through inhibition of altered liver cell foci and hepatic nodule growth during the early stages of neoplastic transformation (Bishayee and Chatterjee. 1995). However, in this study vanadium supplementation was done during the entire course of our experiment and it was not possible to ascertain at which time point this trace element was most effective. In order to explore this area, we initiated a new series of experiments in which the anticarcinogenic potential of vanadium was critically examined before the initiation as well as during the early promotion phase of experimentally induced hepatocarcinogenesis. Our present study is an attempt to gain more quantitative information regarding the morphometric analysis of y-glutamyltranspeptidase (GGT)-positive hepatocyte foci and nodules together with remodelling and altered enzyme activities of GGT in the presence or absence of vanadium during DENA-induced hepatocarcinogenesis in rats. The rationale behind the selection of these parameters lies in the fact that hepatocyte foci demonstrating altered enzyme phenotypes including GGT expression are generally acce...