title: Prenatal TCDD exposure predisposes for mammary cancer in rats.
abstract: Epidemiological data are conflicting in the link between 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) exposure and breast cancer causation. We have hypothesized that timing of exposure to endocrine disruptors, such as TCDD, will alter breast cancer susceptibility. Using a carcinogen induced rat mammary cancer model, we have shown that prenatal exposure to TCDD alters mammary gland differentiation and increases susceptibility for mammary cancer. Investigations into imprinting via DNA methylation mechanisms showed that there were no changes in protein expression in DNA methyltransferases, ER-alpha, ER-beta, GST-pi, or MDGI. Using 2D gels and mass spectrometry, we have found seven proteins to be differentially regulated, including a decrease in superoxide dismutase 1 (SOD1). Down-regulation of SOD1 could provide an environment ill equipped to deal with subsequent free radical exposure. We conclude that prenatal TCDD can predispose for mammary cancer susceptibility in the adult offspring by altering the mammary proteome.
authors.affiliation: Department of Pharmacology and Toxicology, University of Alabama at Birmingham, Birmingham, AL, USA. Jenkinss@uab.edu
authors.forename: Sarah
authors.initials: S
authors.lastname: Jenkins
authors.forename: Craig
authors.initials: C
authors.lastname: Rowell
authors.forename: Jun
authors.initials: J
authors.lastname: Wang
authors.forename: Coral A
authors.initials: CA
authors.lastname: Lamartiniere
mesh_terms: D000818:Animals; D015180:Electrophoresis, Gel, Two-Dimensional; D004785:Environmental Pollutants / Q000633:toxicity; D005260:Female; D015674:Mammary Neoplasms, Animal / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology; D000072317:Polychlorinated Dibenzodioxins / Q000633:toxicity*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D051381:Rats; D013482:Superoxide Dismutase / Q000378:metabolism; D000072105:Superoxide Dismutase-1
chemical_list: D004785:Environmental Pollutants; D000072317:Polychlorinated Dibenzodioxins; C000606292:Sod1 protein, rat; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1