2004
DOI: 10.1093/toxsci/kfh062
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A Novel Effect of Dioxin: Exposure during Pregnancy Severely Impairs Mammary Gland Differentiation

Abstract: Many ligands for the aryl hydrocarbon receptor (AhR) are considered endocrine disruptors and carcinogens, and assessment of adverse health effects in humans exposed to such chemicals has often focused on malignancies, including breast cancer. Mammary tissue contains the AhR, and inappropriate activation of the AhR during fetal development causes defects in mammary development that persist into adulthood. However, it is not known whether the extensive differentiation of mammary tissue that occurs during pregnan… Show more

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Cited by 102 publications
(95 citation statements)
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“…The STAT5 target gene product, whey acidic protein (WAP), was also reported to be down-regulated at the mRNA level by MC in mouse liver in an AHR-dependent manner (Nukaya et al, 2004). Using two primer sets for RT-PCR analysis, we could not detect WAP mRNA in mouse liver, consistent with the selective expression of WAP mRNA in mammary tissue (Vorderstrasse et al, 2004). We suggest that some mouse hepatic genes that are regulated by the GHR-JAK2-STAT5b pathway (e.g., Cyp2d9 and Mup2), but not others (e.g., Cis), are targeted for suppression by PAHs.…”
Section: Discussionmentioning
confidence: 64%
“…The STAT5 target gene product, whey acidic protein (WAP), was also reported to be down-regulated at the mRNA level by MC in mouse liver in an AHR-dependent manner (Nukaya et al, 2004). Using two primer sets for RT-PCR analysis, we could not detect WAP mRNA in mouse liver, consistent with the selective expression of WAP mRNA in mammary tissue (Vorderstrasse et al, 2004). We suggest that some mouse hepatic genes that are regulated by the GHR-JAK2-STAT5b pathway (e.g., Cyp2d9 and Mup2), but not others (e.g., Cis), are targeted for suppression by PAHs.…”
Section: Discussionmentioning
confidence: 64%
“…This dose produced no overt toxicity in previous studies that utilized gd 18 data collection (Holladay et al, 1991) or in pups cross-fostered to naïve dams (Blaylock et al, 1992), suggesting sufficient postnatal TCDD exposure occurred by lactation to induce the wasting syndrome. Alternately, the higher dose of TCDD may have diminished lactation due to impaired mammary gland differentiation (Vorderstrasse et al, 2004). The other treatment groups did not show any significant mortality.…”
Section: Prenatal 10 µG/kg Tcdd Exposure Resulted In Postnatal Mortalitymentioning
confidence: 90%
“…Prototypical environmental pollutants found in industrial pollution, tobacco smoke, and cooked foods include the polycyclic polyhalogenated 2,3,7,8-tetrachlorodibenzo-pdioxin (TCDD), which has been shown to alter mammary gland development (7,8), disrupt endocrine functions (9,10), and promote tumor growth (11,12). Population studies detected the accumulation of TCDD in breast milk (13,14), suggesting that this agent may reach breast tissue and be a risk factor in mammary neoplasia.…”
Section: Introductionmentioning
confidence: 99%