Transplacental carcinogenesis with dibenzo[def,p]chrysene (DBC): Timing of maternal exposures determines target tissue response in offspring

Lyndsey E. Shorey; David J. Castro; William M. Baird; Lisbeth K. Siddens; Christiane V. Löhr; Melissa M. Matzke; Katrina M. Waters; Richard A. Corley; David E. Williams

doi:10.1016/j.canlet.2011.11.010

Transplacental carcinogenesis with dibenzo[def,p]chrysene (DBC): Timing of maternal exposures determines target tissue response in offspring

Lyndsey E. Shorey, David J. Castro, William M. Baird, Lisbeth K. Siddens, Christiane V. Löhr, Melissa M. Matzke, Katrina M. Waters, Richard A. Corley, David E. Williams

Research output: Contribution to journal › Article › peer-review

25 Scopus citations

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). [ ¹⁴C]-DBC (GD 17) dosing revealed transplacental distribution to fetal tissues at 10-fold lower concentrations than in paired maternal tissue and residual [ ¹⁴C] 3weeks post-dose. This study highlights the importance of developmental stage in susceptibility to environmental carcinogens.

Original language	English (US)
Pages (from-to)	49-55
Number of pages	7
Journal	Cancer Letters
Volume	317
Issue number	1
DOIs	https://doi.org/10.1016/j.canlet.2011.11.010
State	Published - Apr 1 2012
Externally published	Yes

Keywords

Carcinogenesis
Fetal
Maternal
PAHs
T-cell lymphoma
Transplacental cancer

ASJC Scopus subject areas

Oncology
Cancer Research

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10.1016/j.canlet.2011.11.010

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title = "Transplacental carcinogenesis with dibenzo[def,p]chrysene (DBC): Timing of maternal exposures determines target tissue response in offspring",

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). [ 14C]-DBC (GD 17) dosing revealed transplacental distribution to fetal tissues at 10-fold lower concentrations than in paired maternal tissue and residual [ 14C] 3weeks post-dose. This study highlights the importance of developmental stage in susceptibility to environmental carcinogens.",

keywords = "Carcinogenesis, Fetal, Maternal, PAHs, T-cell lymphoma, Transplacental cancer",

author = "Shorey, {Lyndsey E.} and Castro, {David J.} and Baird, {William M.} and Siddens, {Lisbeth K.} and L{\"o}hr, {Christiane V.} and Matzke, {Melissa M.} and Waters, {Katrina M.} and Corley, {Richard A.} and Williams, {David E.}",

note = "Funding Information: The authors would like to thank Marilyn Henderson, Tammie McQuistan, and Abby Benninghoff for their technical expertise and Mandy Louderback for animal handling assistance. In addition, we would like to acknowledge Dr. Clifford Pereira, Department of Statistics, Oregon State University, for his advice on statistical modeling. Support from this study was provided by the following PHS Grants from NIH, P42 ES016465 , P01 CA90890 , T32ES07060 and P30 ES03850 along with assistance from The Linus Pauling Institute at Oregon State University. ",

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T1 - Transplacental carcinogenesis with dibenzo[def,p]chrysene (DBC)

T2 - Timing of maternal exposures determines target tissue response in offspring

AU - Shorey, Lyndsey E.

AU - Castro, David J.

AU - Baird, William M.

AU - Siddens, Lisbeth K.

AU - Löhr, Christiane V.

AU - Matzke, Melissa M.

AU - Waters, Katrina M.

AU - Corley, Richard A.

AU - Williams, David E.

N1 - Funding Information: The authors would like to thank Marilyn Henderson, Tammie McQuistan, and Abby Benninghoff for their technical expertise and Mandy Louderback for animal handling assistance. In addition, we would like to acknowledge Dr. Clifford Pereira, Department of Statistics, Oregon State University, for his advice on statistical modeling. Support from this study was provided by the following PHS Grants from NIH, P42 ES016465 , P01 CA90890 , T32ES07060 and P30 ES03850 along with assistance from The Linus Pauling Institute at Oregon State University.

PY - 2012/4/1

Y1 - 2012/4/1

N2 - 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). [ 14C]-DBC (GD 17) dosing revealed transplacental distribution to fetal tissues at 10-fold lower concentrations than in paired maternal tissue and residual [ 14C] 3weeks post-dose. This study highlights the importance of developmental stage in susceptibility to environmental carcinogens.

AB - 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). [ 14C]-DBC (GD 17) dosing revealed transplacental distribution to fetal tissues at 10-fold lower concentrations than in paired maternal tissue and residual [ 14C] 3weeks post-dose. This study highlights the importance of developmental stage in susceptibility to environmental carcinogens.

KW - Carcinogenesis

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KW - Maternal

KW - PAHs

KW - T-cell lymphoma

KW - Transplacental cancer

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Transplacental carcinogenesis with dibenzo[def,p]chrysene (DBC): Timing of maternal exposures determines target tissue response in offspring

Abstract

Keywords

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