Vanadium, a dietary micronutrient, has recently been found to possess a potent antitumor activity during chemically induced rat liver carcinogenesis. In the present study, attempts have been made to understand the basic mechanism of the antitumor response of vanadium by monitoring its effect on chromosomal aberrations (CA) in rat liver cells during the early preneoplastic steps of diethylnitrosamine (DENA)-induced hepatocarcinogenesis. Supplementary vanadium at 0.5 ppm was found to afford a unique protection against DENA-evoked CA 96 h after DENA injection. Concurrent administration of glutathione (GSH) at 200 mg/kg 2 h before DENA treatment potentiated the suppressive effect of vanadium against CA when the rats were sacrificed 96 h after the carcinogenic insult. Pretreatment nf rate with buthionine sulfoximine (890 mg/kg) and/or diethylmaleate (600 mg/kg) 0.5 or 2 h prior to DENA injection resulted in a significant inhibition of vanadium-mediated protection of CA with a concomitant fall in hepatic GSH level. Rats given injection of bromosulfophthalein (250 mg/kg), a substrate inhibitor of glutathione S-transferase (GST), 0.5 h before DENA treatment displayed a prominent suppression of the protective effect of vanadium on DENA-induced CA. Long-term supplementation of vanadium also triggered protective effect against the induction of CA 15, 30 or 45 days following DENA treatment which was maximally observed on structural aberrations followed by numerical aberrations. At these time points, vanadium was found to lower the mitotic index of hepatic cells which was otherwise elevated with DENA alone. Vanadium restored DENA-dependent decrement in the ratio of polychromatic erythrocytes (PCE) to normochromatic erythrocytes (NCE) in rat liver cells. The DENA-induced increased frequency of micronucleated PCE as well as NCE was also attenuated following vanadium supplementation. The anticlastogenic effect of vanadium was found to be parallel to its ability to induce the activity of hepatic GST with a concurrent induction of hepatic GSH pool which were rather decreased in DENA control group. The results of this study, thus, provide evidence that vanadium-dependent induction of GSH-mediated GST-catalyzed detoxificational capacity of the host is presumably related to its suppressive effect against CA. This may explain, in part, the antitumor efficacy of this trace element.

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