VANADIUM-MEDIATED SUPPRESSION OF DIETHYLNITROSAMINE-INDUCED CHROMOSOMAL-ABERRATIONS IN RAT HEPATOCYTES AND ITS CORRELATION WITH INDUCTION OF HEPATIC GLUTATHIONE AND GLUTATHIONE-S-TRANSFERASE

Vanadium, a dietary micronutrient, has recently been found to possess a potent antitumor activity during chemically induced rat liver carcin ogenesis. In the present study, attempts have been made to understand the basic mechanism of the antitumor response of vanadium by monitorin g its effect on chromosomal aberrations (CA) in rat liver cells during the early preneoplastic steps of diethylnitrosamine (DENA)-induced he patocarcinogenesis. Supplementary vanadium at 0.5 ppm was found to aff ord a unique protection against DENA-evoked CA 96 h after DENA injecti on. Concurrent administration of glutathione (GSH) at 200 mg/kg 2 h be fore DENA treatment potentiated the suppressive effect of vanadium aga inst CA when the rats were sacrificed 96 h after the carcinogenic insu lt. Pretreatment nf rate with buthionine sulfoximine (890 mg/kg) and/o r diethylmaleate (600 mg/kg) 0.5 or 2 h prior to DENA injection result ed in a significant inhibition of vanadium-mediated protection of CA w ith a concomitant fall in hepatic GSH level. Rats given injection of b romosulfophthalein (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. L ong-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 nu merical 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 micronucl eated PCE as well as NCE was also attenuated following vanadium supple mentation. The anticlastogenic effect of vanadium was found to be para llel to its ability to induce the activity of hepatic GST with a concu rrent induction of hepatic GSH pool which were rather decreased in DEN A control group. The results of this study, thus, provide evidence tha t vanadium-dependent induction of GSH-mediated GST-catalyzed detoxific ational capacity of the host is presumably related to its suppressive effect against CA. This may explain, in part, the antitumor efficacy o f this trace element.