title: Influence of omega-3 fatty acids on Tamoxifen-induced suppression of rat mammary carcinogenesis.
abstract: We report here a detailed time course study of the individual and combined chemopreventive effects of Tamoxifen (Tam) and a high fish oil (FO) diet on multiple histologic parameters of mammary carcinogenesis. Groups of female Sprague-Dawley rats were injected ip with 1-methyl-1-nitrosourea at 50 days of age and assigned to either a control diet (20% corn oil [CO]) or a FO-rich diet (10% FO + 10% CO) in the presence and absence of Tam in the diet (0.6 ppm). Rats were sacrificed at weeks 4 (before palpable tumors), 8 and 12 (when ∼90% of control rats had palpable tumors). Our results demonstrate a major effect of Tam in inhibiting the development of early preneoplastic lesions. FO, while having a marginal protective effect of it own, enhanced the antitumor action of Tam on all histologic parameters of carcinogenesis, although the effects of the combination were not statistically different from those of Tam alone. The combination of FO and Tam was the only intervention that induced regression of established preneoplastic lesions. We also found that in contrast to plasma, only target tissue n-3 fatty acids (FAs) levels correlated with select tissue biomarkers of carcinogenesis whose expression was altered in a manner predictive of a protective effect. Our results demonstrating the potentially superior chemopreventive efficacy of Tam and n-3FA have important translational implications. Our data also emphasize the importance of local factors in affecting target tissue levels and biologic effects of n-3FA.
authors.affiliation: Department of Medicine, Pennsylvania State University College of Medicine, Hershey, PA.
authors.forename: Andrea
authors.initials: A
authors.lastname: Manni
authors.forename: John P
authors.initials: JP
authors.lastname: Richie
authors.forename: Haifang
authors.initials: H
authors.lastname: Xu
authors.forename: Sharlene
authors.initials: S
authors.lastname: Washington
authors.forename: Cesar
authors.initials: C
authors.lastname: Aliaga
authors.forename: Richard
authors.initials: R
authors.lastname: Bruggeman
authors.forename: Timothy K
authors.initials: TK
authors.lastname: Cooper
authors.forename: Bogdan
authors.initials: B
authors.lastname: Prokopczyk
authors.forename: Neil
authors.initials: N
authors.lastname: Trushin
authors.forename: Ana
authors.initials: A
authors.lastname: Calcagnotto
authors.forename: Arunangshu
authors.initials: A
authors.lastname: Das
authors.forename: Jason
authors.initials: J
authors.lastname: Liao
authors.forename: Karam
authors.initials: K
authors.lastname: El-Bayoumy
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D014408:Biomarkers, Tumor / Q000378:metabolism; D063646:Carcinogenesis / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D018890:Chemoprevention / Q000379:methods; D004032:Diet; D015525:Fatty Acids, Omega-3 / Q000494:pharmacology*; D005260:Female; D005395:Fish Oils / Q000494:pharmacology; D019394:Ki-67 Antigen / Q000235:genetics; D008321:Mammary Glands, Animal / Q000378:metabolism; D008325:Mammary Neoplasms, Experimental / Q000235:genetics / Q000378:metabolism / Q000517:prevention & control*; D008770:Methylnitrosourea; D011230:Precancerous Conditions / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013629:Tamoxifen / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D015525:Fatty Acids, Omega-3; D005395:Fish Oils; D019394:Ki-67 Antigen; D013629:Tamoxifen; D008770:Methylnitrosourea
keywords: Tamoxifen; biomarkers of carcinogenesis; fish oil; omega-3 fatty acids; rat mammary carcinogenesis