TCDD is one of most toxic dioxins produced as an impurity during the manufacture of certain herbicides and the incineration of municipal and industrial waste. It has been reported that exposure to TCDD can alter the metabolism of exogenous chemicals and endogenous steroids. In this work, we have investigatedthe effect of prenatal exposure to TCDD on the mammary gland’s morphology, and genomic profile during critical stages of development. For this purpose pregnant Sprague Dawley rats received 3ug TCDD/kg of body weight, by gavage, on day 15 post conception. A control group received an equivalent volume of sesame oil. At parturition, the offspring were placed with surrogate dams. We divided the offspring in four groups of 20 females each and sacrificed at 21, 35, 50 and 100 days of age. The mammary glands were removed for morphological and genomic analyses. The morphology was evaluated in whole mount preparations in 10 female offspring per group and the structures quantitated were classified as terminal end buds (TEBs), terminal ducts (TDs), and lobules type 1 (Lob1). Ten offspring were used for RNA extraction. The extracted RNAs were fluorescently labeled for hybridization using the Agilent platform of 60-mer oligo-microarrays containing 22,000 features. The most relevant changes observed were a decrease in the number of TEBs and an increased number of Lob1 in the 21 days of age group, whereas, the most significant genomic changes were observed at 100 days. At this age, we found some functions being over expressed, such as, cell adhesion (Cldn14, Pcdh8), proliferation and differentiation (Fgf2, Cxcl10, Erbb2). At 21 days the genomic changes were less evident, however, genes related to immunity (Cd5, Sh2d2a, Cd3d) and apoptosis (Bcl2a1) were over expressed. Altogether our data show an asynchrony between the morphological changes observed and the expression of a genomic profile that is significantly different to the control group at 100 days of age. (This work was supported by NCI and NIEHS Grant UO1 ES012771).

98th AACR Annual Meeting-- Apr 14-18, 2007; Los Angeles, CA