Resum
1899
Xenobiotics agents such as the bisphenol A (BPA) and benzyl butyl phthalate (BBP) are endocrine disruptors. To further define the effects of BPA and BBP in the mammary gland we have studied the effect of their exposure during the rat’s neonatal and prepubertal period. Pregnant Sprague Dawley rats were maintained on a phytoestrogen-free diet. After delivery the nursing dams were daily gavaged with sesame oil (controls), 250 μg BPA/kg body weight (BW), or 500 mg BBP/kg BW every Monday through Friday from the day of delivery (day 1) to the day of weaning (day 21). Ten female litters per group were euthanized when they reached the ages of 21, 35, 50 and 100days of age. Total RNA from the abdominal mammary gland of each animal was extracted and fluorescently labeled for hybridization to Agilent 60-mer oligo microarrays containing 22,000 features per group. Image analysis was performed using Feature Extraction and ImaGene softwares; data were analyzed using GeneSight software and normalized by Lowess method. We have found that at 50 days of age, that is the end of puberty, the mammary glands from animals treated with BPA, but not those treated with BBP, had significant higher expression levels of 127 genes, including the inhibitor of apoptosis Birc2, genes related to signal transduction (Pkib, PKC theta), and to immune surveillance (complement component C3, cathepsin E, ccl2, ccl17, Cd2, Cd5, IgB, Lat and Syk) as well as 96 unknown genes. Using real time RT-PCR we have validated the genes differentially expressed in the arrays. BPA treatment during the lactational period have modified the genomic profile of the rat mammary in a way that clusters of genes, mainly those controlling immune surveillance, are upmodulated at the end of puberty that is the window of highest susceptibility to chemical carcinogenesis. (Work supported by NIEHS Grant U01 ES012771)
Xenobiotics agents such as the bisphenol A (BPA) and benzyl butyl phthalate (BBP) are endocrine disruptors. To further define the effects of BPA and BBP in the mammary gland we have studied the effect of their exposure during the rat’s neonatal and prepubertal period. Pregnant Sprague Dawley rats were maintained on a phytoestrogen-free diet. After delivery the nursing dams were daily gavaged with sesame oil (controls), 250 μg BPA/kg body weight (BW), or 500 mg BBP/kg BW every Monday through Friday from the day of delivery (day 1) to the day of weaning (day 21). Ten female litters per group were euthanized when they reached the ages of 21, 35, 50 and 100days of age. Total RNA from the abdominal mammary gland of each animal was extracted and fluorescently labeled for hybridization to Agilent 60-mer oligo microarrays containing 22,000 features per group. Image analysis was performed using Feature Extraction and ImaGene softwares; data were analyzed using GeneSight software and normalized by Lowess method. We have found that at 50 days of age, that is the end of puberty, the mammary glands from animals treated with BPA, but not those treated with BBP, had significant higher expression levels of 127 genes, including the inhibitor of apoptosis Birc2, genes related to signal transduction (Pkib, PKC theta), and to immune surveillance (complement component C3, cathepsin E, ccl2, ccl17, Cd2, Cd5, IgB, Lat and Syk) as well as 96 unknown genes. Using real time RT-PCR we have validated the genes differentially expressed in the arrays. BPA treatment during the lactational period have modified the genomic profile of the rat mammary in a way that clusters of genes, mainly those controlling immune surveillance, are upmodulated at the end of puberty that is the window of highest susceptibility to chemical carcinogenesis. (Work supported by NIEHS Grant U01 ES012771)
| Idioma original | Anglès |
|---|---|
| Pàgines (de-a) | 448-448 |
| Nombre de pàgines | 1 |
| Revista | Cancer Research |
| Volum | 66 |
| Número | Supl. 8 |
| Estat de la publicació | Publicada - 15 d’abr. 2006 |