Molecular basis of vanadium-mediated inhibition of hepatocellular preneoplasia during experimental hepatocarcinogenesis in rats

Carcinogen‐induced early DNA lesions and metallothionein (MT) over‐expression have been implicated in cell proliferation and thereby subsequent expression of premalignant phenotype of the cell. We have therefore investigated the chemopreventive potential of vanadium in a multi‐biomarker approach, viz. 8‐hydroxy‐2′‐deoxyguanosines (8‐OHdGs), DNA single‐strand breaks (SSBs), DNA‐protein crosslinks (DPCs), chromosomal aberrations (CAs), in situ MT expression, and cell proliferation in rat liver preneoplasia. Hepatocarcinogenesis was induced in male Sprague–Dawley rats with a single, necrogenic, intraperitoneal (i.p.) injection of diethylnitrosamine (DEN) (200 mg/Kg body weight) at week 4 of the experimental protocol followed by promotion with phenobarbital (PB) (0.05% in basal diet), on and from week 8 and continued till 32 weeks in a long‐term regimen. There was a significant and steady elevation of modified DNA bases 8‐OHdGs (P