Molecular basis of anticlastogenic potential of vanadium in vivo during the early stages of diethylnitrosamine-induced hepatocarcinogenesis in rats.
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 (200mg/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(4)VO(3), +V oxidation state) at a dose of 0.5ppm 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.
Chakraborty
Tridib
T
Division of Biochemistry, Department of Pharmaceutical Technology, Jadavpur University, PO Box 17028, Calcutta 700032, India.
Pandey
Nirupama
N
Chatterjee
Amrita
A
Ghosh
Balaram
B
Rana
Basabi
B
Chatterjee
Malay
M
D000080242:8-Hydroxy-2'-Deoxyguanosine; D000818:Animals; D016587:Antimutagenic Agents / Q000494:pharmacology*; D002869:Chromosome Aberrations; D004249:DNA Damage; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000378:metabolism; D004052:Diethylnitrosamine / Q000633:toxicity*; D008114:Liver Neoplasms, Experimental / Q000139:chemically induced* / Q000235:genetics / Q000378:metabolism / Q000517:prevention & control*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D014638:Vanadates / Q000494:pharmacology; D014639:Vanadium / Q000494:pharmacology*
D016587:Antimutagenic Agents; D014639:Vanadium; D004052:Diethylnitrosamine; D014638:Vanadates; D000080242:8-Hydroxy-2'-Deoxyguanosine; C101036:ammonium metavanadate; D003849:Deoxyguanosine