1 alpha,25-dihydroxyvitamin D-3 inhibits rat liver ultrastructural changesin diethylnitrosamine-initiated and phenobarbital promoted rat hepatocarcinogenesis

The active metabolite of vitamin D, 1 alpha ,25-dihydroxyvitamin D-3[1,25(O H)(2)D-3] has been receiving increasing attention and has come to the foref ront of cancer chemoprevention research as being a regulator of cellular gr owth, differentiation and death. In the present study, attempts have been m ade to investigate the in vivo chemopreventive effect of 1,25(OH)(2)D-3 in two-stage rat liver carcinogenesis. Hepatocarcinogenesis was initiated with a single intraperitoneal injection of diethylnitrosamine [DEN] (200 mg/kg b. wt.) at week 4. After a brief recovery period of 2 weeks, all the DEN-tr eated rats were given phenobarbital (0.05%) in the basal diet and continued thereafter till the completion of the experiment. The results of our exper iment showed that the rats which received 1,25(OH)(2)D-3 for 14 weeks (0.3 mug/100 muL propylene glycol, per os, twice a week), starting the treatment 4 weeks prior to DEN injection, exhibited maximum protective effect in mai ntaining the normal cellular architecture of the hepatocytes than the group of rats which received this micronutrient for only 9 weeks. Moreover, cont inuous supplementation of 1,25(OH)(2)D-3 maintains the concentration of hep atic microsomal cytochrome P-450 like that of normal vehicle control. Thus, longterm supplementation of 1,25(OH)(2)D-3 significantly (P < 0.001) inhib its hepatic cytosolic lipid peroxidation, thereby protecting the cell membr anes from free-radical mediated damage. These results suggest that 1,25(OH) (2)D-3 is useful in the inhibition of rat liver carcinogenesis. <(c)> 2001 Wiley-Liss, Inc.