Maternal dietary exposure to fiber during pregnancy and mammary tumorigenesis among rat offspring.
Maternal diet during pregnancy has been proposed to modify female offspring's later susceptibility to develop breast cancer; however, most of the dietary factors identified thus far have led to increased risk. To identify dietary factors that might reduce offspring's breast cancer risk, pregnant rat dams were fed diets containing 6% fiber originating either from cellulose (control), or oat, whole wheat or defatted flax flour. At birth, dams were switched to the AIN93 semi-purified diet. Mammary tumor incidence and multiplicity, induced by administering the offspring 5 mg 7,12-dimethylbenz[a]anthracene (DMBA) at the age of 50 days, was reduced in the whole wheat flour-exposed offspring and increased in the defatted flax-exposed offspring. To identify the mechanisms mediating the effects of in utero dietary exposures, changes in mammary gland morphology and gene expression were assessed before puberty onset (3 weeks of age) and at the time rats are most susceptible to malignant transformation (8 weeks of age). The number of terminal end buds (TEBs), i.e., the targets of malignant transformation, was reduced in the mammary glands of whole wheat- and oat flour-exposed offspring, as compared to the controls. Further, the number of apoptotic epithelial cells (based on ISOL assay) was elevated in the whole wheat flour offspring, but no changes in cell proliferation (PCNA), estrogen receptor alpha (ER-alpha) or cyclin D1 mRNA or protein levels were seen. The mRNA and/or protein levels of BRCA1 and p53 were significantly increased in the mammary glands of whole wheat flour offspring. Further, the levels of 8-hydroxy-2'-deoxyguanosine (8-OHdG), a marker of DNA damage, were significantly reduced in these rats, suggesting that maternal dietary exposure to whole wheat during pregnancy may reduce offspring's breast cancer risk by improving DNA damage repair mechanisms.
Yu
Bin
B
Lombardi Cancer Center and Department of Oncology, Georgetown University, NW, Washington, DC.
Khan
Galam
G
Foxworth
Aaron
A
Huang
Kai
K
Hilakivi-Clarke
Leena
L
D000080242:8-Hydroxy-2'-Deoxyguanosine; D015127:9,10-Dimethyl-1,2-benzanthracene; D000818:Animals; D016588:Anticarcinogenic Agents / Q000008:administration & dosage* / Q000494:pharmacology*; D018554:Avena; D014408:Biomarkers, Tumor / Q000378:metabolism; D002482:Cellulose / Q000008:administration & dosage; D004249:DNA Damage; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000378:metabolism; D004043:Dietary Fiber / Q000008:administration & dosage* / Q000494:pharmacology*; D005260:Female; D019597:Flax / Q000009:adverse effects; D019398:Genes, BRCA1; D008325:Mammary Neoplasms, Experimental / Q000139:chemically induced / Q000378:metabolism / Q000517:prevention & control*; D018811:Maternal Exposure; D011247:Pregnancy; D011270:Pregnancy, Animal; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D014908:Triticum; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
D016588:Anticarcinogenic Agents; D014408:Biomarkers, Tumor; D004043:Dietary Fiber; D012333:RNA, Messenger; D016159:Tumor Suppressor Protein p53; D015127:9,10-Dimethyl-1,2-benzanthracene; D000080242:8-Hydroxy-2'-Deoxyguanosine; D002482:Cellulose; D003849:Deoxyguanosine