Title | Transplacental carcinogenesis with dibenzo[def,p]chrysene (DBC): timing of maternal exposures determines target tissue response in offspring. |
Publication Type | Journal Article |
Year of Publication | 2012 |
Authors | Shorey, LE, Castro, DJ, Baird, WM, Siddens, LK, Löhr, CV, Matzke, MM, Waters, KM, Corley, RA, Williams, DE |
Journal | Cancer Lett |
Volume | 317 |
Issue | 1 |
Pagination | 49-55 |
Date Published | 2012 Apr 1 |
ISSN | 1872-7980 |
Keywords | Animals, Aryl Hydrocarbon Hydroxylases, Benzopyrenes, Carcinogens, Cytochrome P-450 CYP1B1, Female, Fetus, Gene Expression Regulation, Developmental, Gene Expression Regulation, Enzymologic, Gestational Age, Male, Maternal Exposure, Maternal-Fetal Exchange, Mice, Mice, 129 Strain, Neoplasms, Experimental, Placental Circulation, Pregnancy, Prenatal Exposure Delayed Effects, Time Factors, Tissue Distribution |
Abstract | Dibenzo[def,p]chrysene (DBC) is a transplacental carcinogen in mice (15mg/kg; gestation day (GD) 17). To mimic residual exposure throughout pregnancy, dams received four smaller doses of DBC (3.75mg/kg) on GD 5, 9, 13 and 17. This regimen alleviated the previously established carcinogenic responses in the thymus, lung, and liver. However, there was a marked increase in ovarian tumors (females) and hyperplastic testes (males). [(14)C]-DBC (GD 17) dosing revealed transplacental distribution to fetal tissues at 10-fold lower concentrations than in paired maternal tissue and residual [(14)C] 3weeks post-dose. This study highlights the importance of developmental stage in susceptibility to environmental carcinogens.
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DOI | 10.1016/j.canlet.2011.11.010 |
Alternate Journal | Cancer Lett. |
PubMed ID | 22085489 |
PubMed Central ID | PMC3269513 |
Grant List | P01 CA090890 / CA / NCI NIH HHS / United States P01 CA090890-07 / CA / NCI NIH HHS / United States P01 CA90890 / CA / NCI NIH HHS / United States P30 ES000210 / ES / NIEHS NIH HHS / United States P30 ES000210-38 / ES / NIEHS NIH HHS / United States P30 ES03850 / ES / NIEHS NIH HHS / United States P42 ES016465 / ES / NIEHS NIH HHS / United States P42 ES016465 / ES / NIEHS NIH HHS / United States P42 ES016465-02 / ES / NIEHS NIH HHS / United States T32 ES007060 / ES / NIEHS NIH HHS / United States T32 ES007060-30 / ES / NIEHS NIH HHS / United States T32ES07060 / ES / NIEHS NIH HHS / United States |