ABSTRACT: Prenatal exposure to bisphenol A, genistein and indole-3-carbinol on early mammary gland development and carcinogenesis in female Sprague-Dawley offspring
Project description:Rodent studies have indicated that gestational and perinatal bisphenol A (BPA) exposure increase the risk of developing breast cancer during adulthood. In contrast, some dietary compounds such as genistein (GEN) and indole 3-carbinol (I3C) present potential protective effects against inducing hormone-dependent cancers, including that of the mammary gland. Thus, we aimed to evaluate the role of these dietary compounds on early mammary gland development and carcinogenesis in female Sprague-Dawley offspring. Pregnant Sprague-Dawley (SD) rats were treated with BPA at 25 or 250µg/kg b.w./day by gavage from gestational day (GD) 10 to 21 with or without dietary GEN (250 mg/kg chow, ~5.5 mg/kg b.w./day) or I3C (2000 mg/kg chow, ~45.0 mg/kg b.w./day). At post-natal day (PND) 21, some female offspring from different litters were euthanized for mammary gland development and gene expression analyses while other female offspring received a single dose of N-methyl-N-nitrosourea (MNU) for mammary carcinogenesis initiation. The findings this study indicated the prenatal exposure to BPA, GEN and I3C did not significantly alter ductal elongation, number of terminal end buds (TEB) or cell proliferation, and estrogen receptor alpha (ER-α) immunostaining expression in epithelial mammary cells at PND 21. BPA treatment modulated the expression of several genes, but these changes were not associated with a dose dependent response. Dietary GEN and I3C treatment causally and consistent with the mammary gland structures outcomes. Besides, maternal BPA exposure associated with dietary GEN and I3C did not alter the susceptibility to the mammary cancer development in adulthood when the carcinogen was administered in a window of immature mammary gland development.
Project description:Indole-3-carbinol is used as a dietary supplement and has potential use as a therapeutic agent for the prevention of various types of cancer. While substantial evidence exists that indole-3-carbinol can reduce the risk of cancers induced by several known carcinogens when administered to animals, indole-3-carbinol can also function as an initiator and tumor promoter in certain models. The carcinogenic potential of indole-3-carbinol has not been studied in a 2-year bioassay. The objective of the microarray study was to evaluate the transcriptional changes in liver from rats exposed to 0 or 300 mg/kg indole-3-carbinol. At 3 months, livers were analyzed from female Harlan Sprague Dawley rats in the 2-year gavage study of indole-3-carbinol.
Project description:Indole-3-carbinol is used as a dietary supplement and has potential use as a therapeutic agent for the prevention of various types of cancer. While substantial evidence exists that indole-3-carbinol can reduce the risk of cancers induced by several known carcinogens when administered to animals, indole-3-carbinol can also function as an initiator and tumor promoter in certain models. The carcinogenic potential of indole-3-carbinol has not been studied in a 2-year bioassay. The objective of the microarray study was to evaluate the transcriptional changes in liver from rats exposed to 0 or 300 mg/kg indole-3-carbinol. At 3 months, livers were analyzed from female Harlan Sprague Dawley rats in the 2-year gavage study of indole-3-carbinol. Female rats were administered 300 mg indole-3-carbinol/kg body weight in corn oil by gavage, 5 days per week in a 2 year toxicology study of indole-3-carbinol. Gene expression studies were performed on rat liver with samples hybridized to whole rat genome RG230_2.0 rat GeneChip arrays (Affymetrix, CA).
Project description:We previously showed that exposure of rats to environmental cigarette smoke (ECS) causes extensive downregulation of microRNA expression in the lung, resulting in overexpression of multiple genes and proteins. In the present study, we evaluated by microarray the expression of 484 microRNAs in the lung of rats receiving orally chemopreventive agents, including N-acetylcysteine, oltipraz, indole-3-carbinol, 5,6-benzoflavone and phenethyl isothiocyanate, or combinations thereof. Scatterplot, hierarchical cluster, and principal component analyses showed that none of the above chemopreventive regimens appreciably affected the baseline microRNA expression, while all of them attenuated ECS-induced alterations but to a variable extent. Thus, mirnome analysis provides a new tool for predicting both safety and efficacy of cancer chemopreventive agents at early carcinogenesis stages. Keywords: cancer chemoprevention, microRNA, environmental cigarete smoke (ECS), 5,6-benzoflavone (BF), Indole 3-carbinol (I3C),N-acetylcysteine (NAC), oltipraz (OPZ), Phenethyl isothiocyanate (PEITC). Adult male Sprague-Dawley rats (Harlan Italy, Correzzana, Milan, Italy), weighing 315-320 g, were divided into 16 groups, each composed of 8 animals. Half of them were exposed to ECS for 28 consecutive days, as previously described (Izzotti et al., 2005), while the remaining rats (Sham-exposed) were kept for the same period of time in filtered air. The rats belonging to 14 groups were treated with chemopreventive agents, starting 3 days before exposure to ECS.
Project description:Sperm cells from Sprague Dawley male rats fed different high fat diets (lard or corn oil based) and their 50-days-old female offspring mammary gland were used to perfom this array
Project description:We previously showed that exposure of rats to environmental cigarette smoke (ECS) causes extensive downregulation of microRNA expression in the lung, resulting in overexpression of multiple genes and proteins. In the present study, we evaluated by microarray the expression of 484 microRNAs in the lung of rats receiving orally chemopreventive agents, including N-acetylcysteine, oltipraz, indole-3-carbinol, 5,6-benzoflavone and phenethyl isothiocyanate, or combinations thereof. Scatterplot, hierarchical cluster, and principal component analyses showed that none of the above chemopreventive regimens appreciably affected the baseline microRNA expression, while all of them attenuated ECS-induced alterations but to a variable extent. Thus, mirnome analysis provides a new tool for predicting both safety and efficacy of cancer chemopreventive agents at early carcinogenesis stages. Keywords: cancer chemoprevention, microRNA, environmental cigarete smoke (ECS), 5,6-benzoflavone (BF), Indole 3-carbinol (I3C),N-acetylcysteine (NAC), oltipraz (OPZ), Phenethyl isothiocyanate (PEITC).
Project description:We examined the differential expression of miRNAs in vinyl carbamate (VC)-induced lung tumors in A/J mice and assessed if the chemopreventive agent indole-3-carbinol (I3C) reversed the effects of the carcinogen. Microarray studies revealed some up-regulated microRNAs, but down-regulation of several microRNAs in carcinogen-treated mice relative to vehicle-treated mice. Keywords: Expression micro and control RNA from control treated (3 replicates), vinyl carbamate treated (4 replicates) and vinyl carbamate and indole-3-carbinol treated mice was hybridized versus synthetic human DNA to a custom multi-organism oligonucleotide array.
Project description:Nutritional factors may have a role on the susceptibility of the mammary gland malignant transformation. Here we study the role dietary lipids on development and gene expression profile of Sprague-Dawley rat mammary gland
Project description:Cross-species hybridization analysis of mammary glands during pregnancy and lactation. Results provide insight into putative conserved molecular mechanisms regulating mammary gland development. This study was performed to identify orthologous transcripts that are differentially co-expressed in the mammary gland at 2 stages of development (pregnancy and lactation) in wild type Sprague-Dawley rats.
