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Transplacental carcinogenesis with dibenzo[def,p]chrysene (DBC): timing of maternal exposures determines target

Lyndsey E Shorey1, David J Castro, William M Baird

  • 1Department of Environmental and Molecular Toxicology, Oregon State University, Corvallis, OR 97331, USA.

Cancer Letters
|November 17, 2011
PubMed

Insights

Dibenzo[def,p]chrysene (DBC) exposure during pregnancy shifted carcinogenic effects from fetal organs to maternal ovaries and testes in mice. Developmental stage significantly impacts susceptibility to environmental carcinogens.

Area of Science:

  • Environmental Toxicology
  • Developmental Toxicology
  • Carcinogenesis

Background:

  • Dibenzo[def,p]chrysene (DBC) is a known transplacental carcinogen.
  • Previous studies established DBC's carcinogenicity at a single high dose during gestation day 17 in mice.

Purpose of the Study:

  • To investigate the effects of a modified, lower-dose DBC exposure regimen mimicking residual exposure throughout pregnancy.
  • To assess the impact of developmental stage on susceptibility to DBC-induced carcinogenesis.

Main Methods:

  • Pregnant mice received four smaller doses of DBC (3.75mg/kg) on gestation days 5, 9, 13, and 17.
  • Radioactive [(14)C]-DBC was administered on gestation day 17 to track transplacental distribution.
  • Tissue samples were analyzed for tumors and residual radioactivity.

Main Results:

  • The modified DBC regimen alleviated carcinogenic responses in fetal thymus, lung, and liver.
  • A significant increase in ovarian tumors in females and hyperplastic testes in males was observed.
  • Transplacental distribution of [(14)C]-DBC to fetal tissues was 10-fold lower than in maternal tissues, with residual radioactivity persisting for 3 weeks.

Conclusions:

  • Altering the dosing regimen of DBC during pregnancy can shift carcinogenic effects from fetal to maternal tissues.
  • Developmental stage is a critical factor influencing an organism's susceptibility to environmental carcinogens.
  • This study underscores the importance of considering exposure timing and dose when evaluating the risks of environmental carcinogens.

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