Combinatorial effect of fish oil (Maxepa) and 1α,25-dihydroxyvitamin D3 in the chemoprevention of DMBA-induced mammary carcinogenesis in rats

The present study demonstrates the anti-tumor effects of combined supplementations of dietary fish oil (Maxepa) and 1a,25-dihydroxyvitamin D-3 (vitamin D-3) on 7,12-dimethylbenz(a)anthracene (DMBA)-induced rat mammary carcinogenesis. Female Sprague-Dawley rats at 50 days of age were treated with 7,12-dimethylbenz(alpha)anthracene (DMBA; 0.5 mg/100 g body weight) by a single tail vein injection in an oil emulsion. Both fish oil (rich in EPA and DHA) and vitamin D-3 were administered orally at a dose of 0.5 ml/day/rat and 0.3 mu g/100 mu L propylene glycol twice a week respectively and continued to 35 weeks after DMBA administration. Fish oil in combination with vitamin D-3 resulted in a significant reduction in incidence, multiplicity and volume of mammary tumors. These supplementation also inhibited DMBA-induced mammary 7-methylguanine DNA adducts formation, which was measured by HPLC-fluorescence assay (at four sequential time points; ANOVA, F=42.56, P<0.0001). Immunohistochemical analysis revealed that the effect of fish oil and vitamin D-3 occurred through suppression of cell proliferation (BrdU-LI: P<0.0001). Fish oil and vitamin D-3 together also reduced the mRNA expression of iNOS (84%, P<0.05). In view of their natural availability, non-toxicity and acceptability: combined supplementation of fish oil and vitamin D-3 might be effective for chemoprevention of mammary carcinogenesis. (C) 2010 Elsevier Ireland Ltd. All rights reserved.