Molecular basis of anticlastogenic potential of vanadium in vivo during the early stages of diethylnitrosamine-induced hepatocarcinogenesis in rats

Abstract

Carcinogen-induced DNA base modification and subsequent DNA lesions are the critical events for the expression of premalignant phenotype of the cell. We have therefore investigated the chemopreventive efficacy of a vanadium salt against diethylnitrosamine (DEN)-induced early DNA and chromosomal damages in rat liver. Hepatocarcinogenesis was induced in male Sprague–Dawley rats with a single, necrogenic, intraperitoneal injection of DEN (200 mg/kg body weight). 8-Hydroxy-2′-deoxyguanosines (8-OHdGs), strand-breaks and DNA–protein crosslinks (DPCs) were measured by HPLC, comet assay and spectrofluorimetry, respectively. There was a significant and steady elevation of modified bases 8-OHdGs along with substantial increments of the extent of single-strand-breaks (SSBs), DPCs and chromosomal aberrations (CAs) following DEN exposure. Supplementation of vanadium as ammonium metavanadate (NH 4VO 3, +V oxidation state) at a dose of 0.5 ppm in terms of the salt weight throughout the experiment abated the formations of 8-OHdGs ( P < 0.0001; 79.54%), tailed DNA ( P < 0.05; 31.55%) and length:width of DNA mass ( P < 0.02; 61.25%) in preneoplastic rat liver. Vanadium treatment also inhibited DPCs ( P < 0.0001; 58.47%) and CAs ( P < 0.001; 45.17%) studied at various time points. The results indicate that the anticlastogenic potential of vanadium in vivo might be due to the observed reductions in liver-specific 8-OHdGs, SSBs and/or DPCs by this trace metal. We conclude that, vanadium plays a significant role in limiting DEN-induced genotoxicity and clastogenicity during the early stages of hepatocarcinogenesis in rats.