Maternal flaxseed diet during pregnancy or lactation increases female rat offspring's susceptibility to carcinogen-induced mammary tumorigenesis.

Full Abstract

Flaxseed contains several dietary components that have been linked to low breast cancer risk; i.e., n-3 polyunsaturated fatty acids (PUFAs), lignans and fiber, but it also contains detectable levels of cadmium, a heavy metal that activates the estrogen receptor (ER). Since estrogenic exposures early in life modify susceptibility to develop breast cancer, we wondered whether maternal dietary intake of 5% or 10% flaxseed during pregnancy or lactation (between postpartum days 5 and 25) might affect 7,12-dimethylbenz[a]anthracene (DMBA)-induced mammary tumorigenesis in the rat offspring. Our data indicated that both in utero and postnatal 5% and 10% flaxseed exposures shortened mammary tumor latency, and 10% flaxseed exposure increased tumor multiplicity, compared to the controls. Further, when assessed in 8-week-old rats, in utero 10% flaxseed exposure increased lobular ER-alpha protein levels, and both in utero and postnatal flaxseed exposures dose-dependently reduced ER-beta protein levels in the terminal end buds (TEBs) lobules and ducts. Exposures to flaxseed did not alter the number of TEBs or affect cell proliferation within the epithelial structures. In a separate group of immature rats that were fed 5% defatted flaxseed diet (flaxseed source different than in the diets fed to pregnant or lactating rats) for 7 days, cadmium exposure through the diet was six-fold higher than allowed for humans by World Health Organization, and cadmium significantly accumulated in the liver and kidneys of the rats. It remains to be determined whether the increased mammary cancer in rats exposed to flaxseed through a maternal diet in utero or lactation was caused by cadmium present in flaxseed, and whether the reduced mammary ER-beta content was causally linked to increased mammary cancer risk among the offspring.

Learn Faster Today Improve your study skills

Author information

Author/s: Khan, Galam (G); Penttinen, Pauliina (P); Cabanes, Anna (A); Foxworth, Aaron (A); Chezek, Antonia (A); Mastropole, Kristen (K); Yu, Bin (B); Smeds, Annika (A); Halttunen, Teemu (T); Good, Carolyn (C); Mäkelä, Sari (S); Hilakivi-Clarke, Leena (L);

Affiliation: Lombardi Cancer Center, Department of Oncology, Georgetown University, 3970 Reservoir Rd., NW, Washington, DC 20057, USA.

Journal and publication information

Publication Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't

Journal: Reproductive toxicology (Elmsford, N.Y.) (Reprod Toxicol), published in United States. (Language: eng)

Reference: -2007 Apr-May; vol 23 (issue 3) : pp 397-406

Dates: Created 2007/04/24; Completed 2007/09/20;

PMID: 17398067, status: MEDLINE (last retrieval date: 12/26/2008)

Sourced from the National Library of Medicine. Abstract text and other information may be subject to copyright.

External Links for this article (including full text providers, if available):

Click Electronic Full-text Provider Links to see options for finding the electronic full text links to this article. Note there may be a subscription or fee required for access to the full text. See our FAQ for information on finding FREE full text articles.

This article may also be located in paper journal collections available in many libraries. Use the Journal and Publication Information above to find the full article.

MeSH headings (categories)

This article was linked to the MESH Headings shown below.

4-Butyrolactone - analogs & derivatives; metabolism
9,10-Dimethyl-1,2-benzanthracene - administration & dosage; toxicity
Adenocarcinoma - chemically induced; metabolism; pathology
Animals
Animals, Newborn
Butylene Glycols - metabolism
Cadmium - administration & dosage; toxicity
Dose-Response Relationship, Drug
Drug Synergism
Female
Flax - chemistry
Kidney - drug effects; metabolism; pathology

Lactation
Lignans - metabolism
Liver - drug effects; metabolism; pathology
Mammary Glands, Animal - drug effects; metabolism; pathology
Mammary Neoplasms, Animal - chemically induced; metabolism; pathology
Plant Preparations - administration & dosage; chemistry; toxicity
Pregnancy
Prenatal Exposure Delayed Effects
Proliferating Cell Nuclear Antigen - metabolism
Rats
Rats, Sprague-Dawley
Receptors, Estrogen - metabolism

Associated Chemicals: Butylene Glycols (0) ; Lignans (0) ; Plant Preparations (0) ; Proliferating Cell Nuclear Antigen (0) ; Receptors, Estrogen (0) ; secoisolariciresinol (29388-59-8) ; 9,10-Dimethyl-1,2-benzanthracene (57-97-6) ; Cadmium (7440-43-9) ; 2,3-bis(3'-hydroxybenzyl)butyrolactone (76543-15-2) ; 2,3-bis(3'-hydroxybenzyl)butane-1,4-diol (76543-16-3) ; 4-Butyrolactone (96-48-0)

These are the highest related articles currently in the database:

See 100+ related articles.