TitleTransplacental carcinogenesis with dibenzo[def,p]chrysene (DBC): timing of maternal exposures determines target tissue response in offspring.
Publication TypeJournal Article
Year of Publication2012
AuthorsShorey LE, Castro DJ, Baird WM, Siddens LK, Löhr CV, Matzke MM, Waters KM, Corley RA, Williams DE
JournalCancer Lett
Volume317
Issue1
Pagination49-55
Date Published2012 Apr 01
ISSN1872-7980
KeywordsAnimals, 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.

DOI10.1016/j.canlet.2011.11.010
Alternate JournalCancer Lett.
PubMed ID22085489
PubMed Central IDPMC3269513
Grant ListP01 CA090890 / CA / NCI NIH HHS / United States
T32 ES007060-30 / ES / NIEHS NIH HHS / United States
P30 ES003850 / ES / NIEHS NIH HHS / United States
P30 ES03850 / ES / NIEHS NIH HHS / United States
P01 CA90890 / CA / NCI NIH HHS / United States
T32ES07060 / ES / NIEHS NIH HHS / United States
P42 ES016465-02 / ES / NIEHS NIH HHS / United States
P30 ES000210-38 / ES / NIEHS NIH HHS / United States
P42 ES016465 / ES / NIEHS NIH HHS / United States
P01 CA090890-07 / CA / NCI NIH HHS / United States
T32 ES007060 / ES / NIEHS NIH HHS / United States
P30 ES000210 / ES / NIEHS NIH HHS / United States