Combinatorial effect of fish oil (Maxepa) and 1alpha,25-dihydroxyvitamin D(3) 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 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.
Chatterjee
Mary
M
Chemical Carcinogenesis and Chemoprevention Laboratory, Division of Biochemistry, Department of Pharmaceutical Technology, Jadavpur University, Calcutta (Kolkata) 700 032, West Bengal, India. mcbiochem@yahoo.com
Janarthan
M
M
Manivannan
R
R
Rana
Ajay
A
Chatterjee
Malay
M
D015127:9,10-Dimethyl-1,2-benzanthracene / Q000633:toxicity*; D000818:Animals; D001483:Base Sequence; D001973:Bromodeoxyuridine / Q000378:metabolism; D002117:Calcitriol / Q000494:pharmacology*; D002273:Carcinogens / Q000633:toxicity*; D049109:Cell Proliferation; D017931:DNA Primers; D005260:Female; D005395:Fish Oils / Q000494:pharmacology*; D008325:Mammary Neoplasms, Experimental / Q000201:enzymology / Q000473:pathology / Q000517:prevention & control*; D052247:Nitric Oxide Synthase Type II / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley
D002273:Carcinogens; D017931:DNA Primers; D005395:Fish Oils; D012333:RNA, Messenger; D015127:9,10-Dimethyl-1,2-benzanthracene; D052247:Nitric Oxide Synthase Type II; D002117:Calcitriol; D001973:Bromodeoxyuridine