Inhibition of diethylnitrosamine-induced rat liver chromosomal aberrationsand DNA-strand breaks by synergistic supplementation of vanadium and 1 alpha,25-dihydroxyvitamin D-3

Vanadium (V) has recently been found to possess potent anti-neoplastic acti vity in rat hepatocarcinogenesis. Recent studies have suggested that the ac tive metabolite of vitamin D-3, 1 alpha ,25-dihydroxyvitamin D-3 [1,25(OH)( 2)D-3], can inhibit growth and/or induce differentiation of a variety of ce ll types. In the present study, attempts have been made to investigate the combination effects on chromosomal aberrations (CAs) and DNA-strand breaks during the early preneoplastic stage of diethylnitrosamine (DEN)-induced ra t liver carcinogenesis in male Sprague-Dawley rats. V (0.5 ppm ad libitum) and/or 1,25(OH)(2)D-3 (0.3 mug/0.1 mi propylene glycol per os twice weekly) either alone or in combination were given to I)EN-treated and control rats 4 weeks prior to DEN injection. Under these experimental conditions it was observed that, when given in combination, V and 1,25(OH)(2)D-3 offered max imum protection against DEN-induced structural aberrations 96 h (66.7%, P < 0.05), 15 days (44.9%, P < 0.005) and 30 days (63.8%, P < 0.001) after DEN injection. Synergistic supplementation of both V and 1,25(OH)(2)D-3 1 week s before DEN injection was found to offer significant (64.1%, P < 0.001) pr otection against generation of single-strand breaks when compared with the DEN control. Thus, the combination effect of V, an essential trace element, and of 1,25(OH)(2)D-3, a dietary micronutrient, appears beneficial in prev enting genetic damage in liver cells upon alkylation induced by DEN. (C) 20 00 Elsevier Science B.V. All rights reserved.