Inhibition of diethylnitrosamine-induced rat liver chromosomal aberrations and DNA-strand breaks by synergistic supplementation of vanadium and 1alpha,25-dihydroxyvitamin D(3).
Vanadium (V) has recently been found to possess potent anti-neoplastic activity in rat hepatocarcinogenesis. Recent studies have suggested that the active metabolite of vitamin D(3), 1alpha, 25-dihydroxyvitamin D(3) [1,25(OH)(2)D(3)], can inhibit growth and/or induce differentiation of a variety of cell 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 rat liver carcinogenesis in male Sprague-Dawley rats. V (0.5 ppm ad libitum) and/or 1,25(OH)(2)D(3) (0.3 microg/0.1 ml propylene glycol per os twice weekly) either alone or in combination were given to DEN-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 maximum 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) 4 weeks before DEN injection was found to offer significant (64.1%, P<0.001) protection 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 preventing genetic damage in liver cells upon alkylation induced by DEN.
Basak
R
R
Division of Biochemistry, Department of Pharmaceutical Technology, Jadavpur University, PO Box 17028, 700 032, Calcutta, India. ranjan_basak@hotmail.com
Saha
B K
BK
Chatterjee
M
M
D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage; D002117:Calcitriol / Q000008:administration & dosage*; D002869:Chromosome Aberrations; D004249:DNA Damage; D004052:Diethylnitrosamine / Q000037:antagonists & inhibitors* / Q000633:toxicity*; D004357:Drug Synergism; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008114:Liver Neoplasms, Experimental / Q000139:chemically induced / Q000517:prevention & control; D008297:Male; D011230:Precancerous Conditions / Q000139:chemically induced / Q000517:prevention & control; D051381:Rats; D017207:Rats, Sprague-Dawley; D014639:Vanadium / Q000008:administration & dosage*
D000970:Antineoplastic Agents; D014639:Vanadium; D004052:Diethylnitrosamine; D002117:Calcitriol