Combined supplementation of vanadium and 1 alpha,25-dihydroxyvitamin D-3 inhibit diethylnitrosamine-induced rat liver carcinogenesis

A combination of a differentiation-inducing agent like 1 alpha,25-dihydroxy vitamin D-3 [1,25(OH)(2)D-3] with a compound that blocks entry of calcium i nto cells like vanadium (V) may offer a new approach to differentiation the rapy and address the problem of hypercalcemia. Initiation of hepatocarcinog enesis was performed by a single intraperitoneal injection of diethylnitros amine (DEN) (200 mg/kg b.wt.) in male Sprague-Dawley rats. Supplementation of V, 1,25(OH)(2)D-3, or both V and 1,25(OH)(2)D-3 were started 4 weeks pri or to DEN injection and continued thereafter till 20th week. It was observe d that supplementation of V (0.5 ppm) in drinking water ad libitum or 1,25( OH)(2)D-3 (3 mu g/ml propylene glycol) per os twice weekly for the entire p eriod of the experiment significantly reduces the number and size of hyperp lastic nodules while the combination treatment offered an additive effect i n reducing it to 37.5% from 83.3%. V-1,25(OH)(2)D-3 combination was also ef fective in elevating the level of hepatic microsomal cytochrome P-450 (Cyt. P-450) (P < 0.001). Moreover, A significant reduced level of cytosolic glu tathione (GSH) (P < 0.001) and glutathione S-transferase (GST) (P<0.001) ac tivity as well as reduction in thr appearance of gamma-glutamyltranspeptida se (GGT)-positive foci (P<0.001) as compared to carcinogen control were obs erved in V plus 1,25(OH)(2)D-3 treated group. These results suggest that V may be useful in combination with 1,25(OH)(2)D-3 in the inhibition of exper imental rat hepatocarcinogenesis. (C) 2000 Elsevier Science Ireland Ltd. Al l rights reserved.