Mammary gland density predicts the cancer inhibitory activity of the N-3 to N-6 ratio of dietary fat.

Abstract

This study investigated the effect of a broad range of dietary ratios of n-3:n-6 fatty acids on mammary gland density and mammary cancer risk. Cancer was induced in female rats by N-methyl-N-nitrosourea. Purified diet that provided 30% of dietary kilocalories from fat was formulated to contain ratios of n-3:n-6 fatty acids from 25:1 to 1:25. Mammary gland density was determined by digital analysis, fatty acids by gas chromatography/flame ionization detection, and other plasma analytes via ELISA. Mammary gland density was reduced dose dependently at n-3:n-6 ratios from 1:1 to 25:1 (r = -0.477, P = 0.038), with a 20.3% decrease of mammary gland density between n-3:n-6 of 1:1 versus 25:1, P < 0.001. Mammary carcinogenesis was inhibited in the absence or presence of tamoxifen (1 mg/kg diet) in a manner predicted by mammary gland density. Plasma n-3 fatty acid concentrations failed to increase above an n-3:n-6 ratio of 5:1, and changes in specific plasma n-3 or n-6 fatty acids were not predictive of mammary gland density or cancer inhibitory activity. A strong reciprocal effect of the n-3:n-6 ratio on plasma leptin (decreased, P = 0.005) and adiponectin (increased, P < 0.001) was observed indicating adipose tissue function was modulated. However, neither cytokine was predictive of mammary gland density. Plasma insulin-like growth factor I (IGF-I) decreased with increasing dietary n-3:n-6 ratio (P = 0.004) and was predictive of the changes in mammary gland density (r = 0.362, P < 0.005). These findings indicate that (i) mammary gland density predicted the carcinogenic response, (ii) the n-3:n-6 ratio exerts effects in the presence or absence of hormonal regulation of carcinogenesis, and (iii) signaling pathways regulated by IGF-I are potential targets for further mechanistic investigation.

• Authors: Zongjian Zhu, Weiqin Jiang, John N McGinley, Bogden Prokopczyk, John P Richie Jr, Karam El Bayoumy, Andrea Manni, Henry J Thompson
• Journal: Cancer prevention research (Philadelphia, Pa.) (Cancer Prev Res (Phila)) Vol. 4 Issue 10 Pg. 1675-85 (Oct 2011) ISSN: 1940-6215 [Electronic] United States
• PMID: 21813405 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Alkylating Agents
• Antineoplastic Agents, Hormonal
• Cytokines
• Fatty Acids, Omega-3
• Fatty Acids, Omega-6
• Tamoxifen
• Insulin-Like Growth Factor I
• Methylnitrosourea

Topics

• Adipose Tissue (drug effects, metabolism)
• Alkylating Agents (toxicity)
• Animals
• Antineoplastic Agents, Hormonal (pharmacology)
• Cytokines (blood)
• Diet
• Enzyme-Linked Immunosorbent Assay
• Fatty Acids, Omega-3 (metabolism)
• Fatty Acids, Omega-6 (metabolism)
• Female
• Insulin-Like Growth Factor I (metabolism)
• Mammary Glands, Animal (drug effects, pathology)
• Mammary Neoplasms, Experimental (chemically induced, prevention & control)
• Methylnitrosourea (toxicity)
• Rats
• Rats, Sprague-Dawley
• Tamoxifen (pharmacology)