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.
Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.
Publication types
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Research Support, N.I.H., Extramural
MeSH terms
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Animals
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Aryl Hydrocarbon Hydroxylases / genetics
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Aryl Hydrocarbon Hydroxylases / metabolism
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Benzopyrenes / administration & dosage
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Benzopyrenes / pharmacokinetics
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Benzopyrenes / toxicity*
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Carcinogens / administration & dosage
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Carcinogens / pharmacokinetics
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Carcinogens / toxicity*
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Cytochrome P-450 CYP1B1
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Female
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Fetus / drug effects
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Fetus / metabolism
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Gene Expression Regulation, Developmental
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Gene Expression Regulation, Enzymologic
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Gestational Age
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Male
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Maternal Exposure*
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Maternal-Fetal Exchange*
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Mice
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Mice, 129 Strain
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Neoplasms, Experimental / chemically induced*
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Neoplasms, Experimental / pathology
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Placental Circulation*
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Pregnancy
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Prenatal Exposure Delayed Effects*
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Time Factors
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Tissue Distribution
Substances
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Benzopyrenes
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Carcinogens
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Aryl Hydrocarbon Hydroxylases
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Cyp1b1 protein, mouse
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Cytochrome P-450 CYP1B1
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dibenzo(a,l)pyrene