1α, 25-DIHYDROXYVITAMIN D3-MEDIATED INHIBITION OF HEPATOCELLULAR PRENEOPLASIA IN A CHEMICAL CARCINOGENESIS MODEL

Abstract

In this chapter, the chemopreventive potentials of 1α, 25-dihydroxyvitamin D3 were evaluated by assessing metallothionein (MT) expression and cell proliferation together with the levels of formation of oxidative DNA adducts 8-hydroxy-2’-deoxyguanosine (8-OHdG) during the preneoplastic stages of experimental carcinogenesis in a rodent liver model. Hepatocarcinogenesis was initiated by a single, necrogenic, intraperitoneal (i.p.) injection of DEN at a dose of 200 mg/kg body weight followed by administration of phenobarbital (PB) as a carcinogenic promoter, 0.05% in basal diet, 5 days a week, till the end of the experiment. Treatment of 1α, 25-dihydroxyvitamin D3 was given at a dose of 0.3 g / 100 l in propylene glycol, per os, twice a week in a long-term continuous regimen. The formation of 8-OHdG was estimated by HPLC technique, whereas, MT expression and cell proliferation were assessed by enzyme immunohistochemistry. In a short-term regimen, supplementation of 1α, 25-dihydroxyvitamin D3 substantially inhibited the generation of 8-OHdG in preneoplastic rat liver. Moreover, treatment with the active form of Vitamin D3 significantly abated the expression of MT and a strong positive correlation between MT expression and BrdU-labeling was also noticed. Data presented in this study indicate the chemopreventive potential of 1α, 25-dihydroxyvitamin D3 in limiting hepatocellular preneoplasia in a rodent chemical carcinogenesis model.