Combinatorial effect of fish oil (Maxepa) and 1alpha, 25-dihydroxyvitamin D(3) in the chemoprevention of DMBA-induced mammary carcinogenesis in rats.
Chem Biol Interact. 2010 Jun 23. Epub ahead of print
Chatterjee M, Janarthan M, Manivannan R, Rana A, Chatterjee M.
Chemical Carcinogenesis and Chemoprevention Laboratory, Division of Biochemistry, Department of Pharmaceutical Technology, Jadavpur University, Calcutta (Kolkata)-700 032, West Bengal, India.
The present study demonstrates the anti-tumor effects of combined supplementations of dietary fish oil (Maxepa) and 1alpha, 25-dihydroxyvitamin D(3) (vitamin D(3)) on 7,12-dimethylbenz(alpha)anthracene (DMBA) induced rat mammary carcinogenesis. Female Sprague-Dawley rats at 50 days of age were treated with 7,12-dimethylbenz(alpha)anthracene (DMBA; 0.5mg per 100g 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 0.5ml/day/rat and 0.3mug/100muL 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. Copyright © 2010. Published by Elsevier Ireland Ltd. PMID: 20599847