title: Effects of fish oil and Tamoxifen on preneoplastic lesion development and biomarkers of oxidative stress in the early stages of N-methyl-N-nitrosourea-induced rat mammary carcinogenesis.
abstract: Epidemiologic studies on the protective role of omega-3 fatty acids (n:3) on breast cancer prevention remain inconclusive but studies in preclinical models provide more positive outcome. However, the mechanisms accounting for the protective effect of n:3 are not defined. In the present study, conducted in the N-methyl-N-nitrosourea-induced rat mammary carcinogenesis model, we examined the effects of n:3 individually and in combination with the anti-estrogen Tamoxifen (Tam) on a comprehensive panel of systemic and preneoplastic mammary gland restricted biomarkers which may be critical in the progression to invasive cancer. We observed that fish oil (FO) rich diets significantly reduced Ki67 expression in hyperplastic lesions, while cleaved caspase-3 expression was not affected. Dietary FO and/or Tam did not have major effects on systemic oxidative stress biomarkers, based on oxidative damage to DNA measured as 8-hydroxy-2-deoxyguanosine (8-OH-dG) and lipid peroxidation assessed as thiobarbituric acid reactive substances (TBARS). Tissue levels of 8-isoprostane, on the other hand, were markedly reduced (p<0.0001) in FO-fed rats, possibly as a result of FO-induced depletion of arachidonic acid in the mammary gland. These results suggest that the protective effect of n:3 in this experimental system is not mediated by changes in the levels of oxidative stress but may result from suppression of arachidonic acid-specific pathways.
authors: Division of Endocrinology, H044, Hershey Medical Center, Hershey, PA 17033, USA. amanni@hmc.psu.edu
authors: Andrea
authors: A
authors: Manni
authors: John P
authors: JP
authors: Richie
authors: Haifang
authors: H
authors: Xu
authors: Sharlene
authors: S
authors: Washington
authors: Cesar
authors: C
authors: Aliaga
authors: Timothy K
authors: TK
authors: Cooper
authors: Richard
authors: R
authors: Bruggeman
authors: Arunangshu
authors: A
authors: Das
authors: Bogdan
authors: B
authors: Prokopczyk
authors: Ana
authors: A
authors: Calcagnotto
authors: Neil
authors: N
authors: Trushin
authors: Rebecca
authors: R
authors: Dickinson
authors: Jason
authors: J
authors: Liao
authors: Michael F
authors: MF
authors: Verderame
authors: Karam
authors: K
authors: El-Bayoumy
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D053148:Caspase 3 / Q000378:metabolism; D002471:Cell Transformation, Neoplastic / Q000139:chemically induced / Q000187:drug effects / Q000378:metabolism; D004032:Diet; D004789:Enzyme Activation / Q000187:drug effects; D005227:Fatty Acids / Q000378:metabolism; D005260:Female; D005395:Fish Oils / Q000494:pharmacology*; D005978:Glutathione / Q000097:blood; D005979:Glutathione Peroxidase / Q000378:metabolism; D019394:Ki-67 Antigen / Q000378:metabolism; D008321:Mammary Glands, Animal / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008325:Mammary Neoplasms, Experimental / Q000378:metabolism*; D008770:Methylnitrosourea; D018384:Oxidative Stress / Q000187:drug effects*; D011230:Precancerous Conditions / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013629:Tamoxifen / Q000494:pharmacology*; D013997:Time Factors
chemical_list: D015415:Biomarkers; D005227:Fatty Acids; D005395:Fish Oils; D019394:Ki-67 Antigen; D013629:Tamoxifen; D008770:Methylnitrosourea; D005979:Glutathione Peroxidase; D053148:Caspase 3; D005978:Glutathione