title: Maternal western style diet increases susceptibility to chemically-induced mammary carcinogenesis in female rats offspring.
abstract: The present study investigated whether maternal exposure to western style diet (WD) increases susceptibility to mammary carcinogenesis induced by N-methyl-N-nitrosourea (MNU) in female offspring. Pregnant female Sprague-Dawley rats received WD diet or control diet from gestational day 12 until postnatal day (PND) 21. At PND 21, female offspring received a single dose of MNU (50 mg/kg body weight) and were fed chow diet until PND 110. Mammary gland structures were assessed on whole-mount preparations in the offspring at PND 21, and tumor morphology was examined at PND 110. Immunohistochemical analysis for cell proliferation (PCNA), apoptosis (cleaved caspase-3) and estrogen receptor alpha (ER-α) was performed in mammary terminal end buds (TEBs) at PND 21, and PCNA, ER-α, and p63 analysis in mammary tumors at PND 110. Maternal WD intake induced a significant increase in the number of TEBs (P = 0.024) and in PCNA labeling index (P < 0.020) in the mammary glands at PND 21. Tumor multiplicity, tumor weight, and PCNA labeling indexes were significantly higher in the WD offspring than that of the control offspring (P < 0.05). These findings indicate that maternal western style diet potentially enhanced the development of mammary tumors induced by MNU in female offspring, possibly by affecting the mammary gland differentiation.
authors.affiliation: a Department of Pathology, Botucatu Medical School , São Paulo State University , São Paulo , Brazil.
authors.forename: Gisele A D
authors.initials: GA
authors.lastname: Lopes
authors.forename: William Y C
authors.initials: WY
authors.lastname: Fan
authors.forename: Heloisa
authors.initials: H
authors.lastname: Ciol
authors.forename: Lucas T
authors.initials: LT
authors.lastname: Bidinotto
authors.forename: Maria A M
authors.initials: MA
authors.lastname: Rodrigues
authors.forename: Luís F
authors.initials: LF
authors.lastname: Barbisan
mesh_terms: D000818:Animals; D017209:Apoptosis; D063646:Carcinogenesis; D053148:Caspase 3 / Q000235:genetics / Q000378:metabolism; D002454:Cell Differentiation; D049109:Cell Proliferation; D066273:Diet, Western / Q000009:adverse effects*; D004198:Disease Susceptibility / Q000209:etiology; D047628:Estrogen Receptor alpha / Q000235:genetics / Q000378:metabolism; D005260:Female; D008325:Mammary Neoplasms, Experimental / Q000139:chemically induced / Q000473:pathology*; D039382:Maternal Nutritional Physiological Phenomena; D008770:Methylnitrosourea / Q000633:toxicity; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D047628:Estrogen Receptor alpha; D008770:Methylnitrosourea; C505410:Casp3 protein, rat; D053148:Caspase 3