Molecular Basis of Anticlastogenic Potential of Vanadium in Vivo During the Early Stages of Diethylnitrosamine-Induced Hepatocarcinogenesis in Rats
Document Type
Article
Publication Date
10-30-2006
Description
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 (NH4VO3, +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.
Citation Information
Chakraborty, Tridib; Pandey, Nirupama; Chatterjee, Amrita; Ghosh, Balaram; Rana, Basabi; and Chatterjee, Malay. 2006. Molecular Basis of Anticlastogenic Potential of Vanadium in Vivo During the Early Stages of Diethylnitrosamine-Induced Hepatocarcinogenesis in Rats. Mutation Research - Genetic Toxicology and Environmental Mutagenesis. Vol.609(2). 117-128. https://doi.org/10.1016/j.mrgentox.2006.04.023 PMID: 16942905 ISSN: 1383-5718
