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

Andrea Manni, John P. Richie, Haifang Xu, Sharlene Washington, Cesar Aliaga, Timothy K. Cooper, Richard Bruggeman, Arunangshu Das, Bogdan Prokopczyk, Ana Calcagnotto, Neil Trushin, Rebecca Dickinson, Jason Liao, Michael F. Verderame, Karam El-Bayoumy

Research output: Contribution to journalArticle

12 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)1153-1164
Number of pages12
JournalInternational journal of oncology
Volume39
Issue number5
DOIs
StatePublished - Nov 1 2011

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Methylnitrosourea
Fish Oils
Tamoxifen
Carcinogenesis
Oxidative Stress
Breast
Biomarkers
8-epi-prostaglandin F2alpha
Human Mammary Glands
Arachidonic Acid
Unsaturated Dietary Fats
Thiobarbituric Acid Reactive Substances
Omega-3 Fatty Acids
Caspase 3
Lipid Peroxidation
DNA Damage
Epidemiologic Studies
Estrogens
Diet
Neoplasms

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Cite this

@article{a48d3e9b8b1a40c1945479e5dc65385c,
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.",
author = "Andrea Manni and Richie, {John P.} and Haifang Xu and Sharlene Washington and Cesar Aliaga and Cooper, {Timothy K.} and Richard Bruggeman and Arunangshu Das and Bogdan Prokopczyk and Ana Calcagnotto and Neil Trushin and Rebecca Dickinson and Jason Liao and Verderame, {Michael F.} and Karam El-Bayoumy",
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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. / Manni, Andrea; Richie, John P.; Xu, Haifang; Washington, Sharlene; Aliaga, Cesar; Cooper, Timothy K.; Bruggeman, Richard; Das, Arunangshu; Prokopczyk, Bogdan; Calcagnotto, Ana; Trushin, Neil; Dickinson, Rebecca; Liao, Jason; Verderame, Michael F.; El-Bayoumy, Karam.

In: International journal of oncology, Vol. 39, No. 5, 01.11.2011, p. 1153-1164.

Research output: Contribution to journalArticle

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T1 - 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

AU - Manni, Andrea

AU - Richie, John P.

AU - Xu, Haifang

AU - Washington, Sharlene

AU - Aliaga, Cesar

AU - Cooper, Timothy K.

AU - Bruggeman, Richard

AU - Das, Arunangshu

AU - Prokopczyk, Bogdan

AU - Calcagnotto, Ana

AU - Trushin, Neil

AU - Dickinson, Rebecca

AU - Liao, Jason

AU - Verderame, Michael F.

AU - El-Bayoumy, Karam

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