Vanadium suppresses sister-chromatid exchange and DNA-protein crosslink formation and restores antioxidant status and hepatocellular architecture during 2-acetylaminofluorene-induced experimental rat hepatocarcinogenesis.

Abstract

Vanadium is an important regulator of cellular growth, differentiation, and cell death, and thus has received increasing attention to be an effective cancer chemopreventive agent. In the present study, attempts have been made to investigate the in vivo antineoplastic effect of this micronutrient at the 0.5 ppm dosage in drinking water, by monitoring hepatic nodulogenesis and hepatocellular phenotype followed by antioxidant status and atomic absorption spectrometric estimation of some essential biometals during the multistage of carcinogenesis induced by 2-acetylaminofluorene (2-AAF; 0.05% in basal diet). Finally, sister-chromatid exchange (SCE) and DNA-protein crosslink (DPC) formation, as potential biomarkers were estimated to find out the suppressive effect of vanadium at the molecular level. The results showed that vanadium administration throughout the experiment reduced the relative liver weight, nodular incidence (48.40%), total number, and multiplicity (63.91%), and altered the size of visible persistent nodules (PNs) with concurrent restoration of hepatic glutathione (P < 0.01), glutathione-S-transferase (P < 0.001) and manganese-dependent superoxide dismutase (P < 0.001) activities as well as, hepatic zinc and copper contents (P < 0.001) when compared to the carcinogen control. Moreover, vanadium treatment significantly reduced SCE frequency (50.24%) and DPC coefficient (P < 0.001; 21.30%). Our results, thus, strongly suggest that supplementary vanadium at a dose of 0.5 ppm, when administered continuously throughout the study, than administered either in the initiation or promotion phase alone, is very much effective in suppressing neoplastic transformation during 2-AAF-induced in vivo rat hepatocarcinogenesis.