title: Pubertal supplementation of lipotropes in female rats reduces mammary cancer risk by suppressing histone deacetylase 1.
abstract: OBJECTIVE
  The time from puberty to the first pregnancy is known to be important for a woman's life-time breast cancer risk. Recent studies suggest that epigenetic mechanisms may involve pubertal maturation processes, which can affect the risk of breast cancer in later life. Epigenetic alterations are related to lipotropes (methionine, choline, folate, and vitamin B12), which are methyl donors and cofactors. However, the effects of pubertal supplementation of lipotropes in breast cancer remain largely unknown.
  
  
  METHODS
  Twenty female Sprague-Dawley rats, aged 6 weeks, were divided into two groups and fed a normal control diet or a lipotrope-fortified diet formulated to provide five times basal levels of lipotropes during puberty. All rats were injected intraperitoneally with N-nitroso-N-methylurea at 50 days of age to induce mammary tumors.
  
  
  RESULTS
  Tumor multiplicity and tumor volume decreased significantly as a result of lipotrope supplementation. Interestingly, quantitative RT-PCR revealed significantly decreased expression of histone deacetylase 1 (Hdac1) and DNA methyltransferase 1 (Dnmt1) genes in tumor tissues of the rats supplemented with lipotrope-fortified diet, suggesting that reduced risk of breast cancer can be attributed, at least in part, to decreased expression of these two genes.
  
  
  CONCLUSIONS
  This study demonstrates that supplementation of lipotrope-fortified diet during puberty suppresses tumor growth, potentially through down-regulating Hdac1 and Dnmt1 gene expression. Our findings suggest that pubertal methyl diet plays an important role in the etiology of breast cancer, and further studies are warranted to develop preventative strategies against breast cancer.
authors.affiliation: Department of Animal Sciences, North Dakota State University, 1300 Albrecht Avenue, Fargo, ND, 58102, USA, kyongshin.cho@ndsu.edu.
authors.forename: Kyongshin
authors.initials: K
authors.lastname: Cho
authors.forename: Woo-Sik
authors.initials: WS
authors.lastname: Choi
authors.forename: Courtney L
authors.initials: CL
authors.lastname: Crane
authors.forename: Chung S
authors.initials: CS
authors.lastname: Park
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000517:prevention & control*; D002794:Choline / Q000494:pharmacology; D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000235:genetics / Q000378:metabolism; D019587:Dietary Supplements; D015536:Down-Regulation; D005260:Female; D005492:Folic Acid / Q000494:pharmacology; D056284:Histone Deacetylase 1 / Q000235:genetics / Q000378:metabolism*; D008715:Methionine / Q000494:pharmacology; D008770:Methylnitrosourea / Q000009:adverse effects; D018977:Micronutrients / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012307:Risk Factors; D014805:Vitamin B 12 / Q000494:pharmacology
chemical_list: D018977:Micronutrients; D008770:Methylnitrosourea; D005492:Folic Acid; D008715:Methionine; D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases; C000619382:Dnmt1 protein, rat; C515890:Hdac1 protein, rat; D056284:Histone Deacetylase 1; D002794:Choline; D014805:Vitamin B 12