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 Oct 6;188(1):102-10. doi: 10.1016/j.cbi.2010.06.007. Epub 2010 Jun 23.

Abstract

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/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 0.5 ml/day/rat and 0.3 microg/100 microL 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 9,10-Dimethyl-1,2-benzanthracene / toxicity*
  • Animals
  • Base Sequence
  • Bromodeoxyuridine / metabolism
  • Calcitriol / pharmacology*
  • Carcinogens / toxicity*
  • Cell Proliferation
  • DNA Primers
  • Female
  • Fish Oils / pharmacology*
  • Mammary Neoplasms, Experimental / enzymology
  • Mammary Neoplasms, Experimental / pathology
  • Mammary Neoplasms, Experimental / prevention & control*
  • Nitric Oxide Synthase Type II / genetics
  • RNA, Messenger / genetics
  • Rats
  • Rats, Sprague-Dawley

Substances

  • Carcinogens
  • DNA Primers
  • Fish Oils
  • RNA, Messenger
  • 9,10-Dimethyl-1,2-benzanthracene
  • Nitric Oxide Synthase Type II
  • Calcitriol
  • Bromodeoxyuridine