Maternal flaxseed diet during pregnancy or lactation increases female rat offspring's susceptibility to carcinogen-induced mammary tumorigenesis.
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.
Khan
Galam
G
Lombardi Cancer Center, Department of Oncology, Georgetown University, 3970 Reservoir Rd., NW, Washington, DC 20057, USA.
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
D015107:4-Butyrolactone / Q000031:analogs & derivatives / Q000378:metabolism; D015127:9,10-Dimethyl-1,2-benzanthracene / Q000008:administration & dosage / Q000633:toxicity; D000230:Adenocarcinoma / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology; D000818:Animals; D000831:Animals, Newborn; D002072:Butylene Glycols / Q000378:metabolism; D002104:Cadmium / Q000008:administration & dosage / Q000633:toxicity; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D005260:Female; D019597:Flax / Q000737:chemistry*; D007668:Kidney / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D007774:Lactation; D017705:Lignans / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008321:Mammary Glands, Animal / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D015674:Mammary Neoplasms, Animal / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology; D028321:Plant Preparations / Q000008:administration & dosage / Q000737:chemistry / Q000633:toxicity*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011960:Receptors, Estrogen / Q000378:metabolism
D002072:Butylene Glycols; D017705:Lignans; D028321:Plant Preparations; D018809:Proliferating Cell Nuclear Antigen; D011960:Receptors, Estrogen; D002104:Cadmium; D015127:9,10-Dimethyl-1,2-benzanthracene; C029498:2,3-bis(3'-hydroxybenzyl)butane-1,4-diol; C060283:secoisolariciresinol; D015107:4-Butyrolactone; C029497:2,3-bis(3'-hydroxybenzyl)butyrolactone