Tissue distribution and metabolism of benzo[a]pyrene in embryonic and larval medaka (Oryzias latipes)

Michael W. Hornung, Philip M. Cook, Patrick N. Fitzsimmons, Douglas W. Kuehl, John W. Nichols

Research output: Contribution to journalArticlepeer-review

25 Scopus citations

Abstract

The need to understand chemical uptake, distribution, and metabolism in embryonic and larval fish derives from the fact that these early life stages often exhibit greater sensitivity to xenobiotic compounds than do adult animals. In this study, a 6-h acute waterborne exposure immediately after fertilization was used to quickly load the egg with benzo[a]pyrene (BaP). This exposure was used to mimic the initial egg concentration of a persistent bioaccumulative toxicant that could result from maternal transfer. We used multiphoton laser scanning microscopy (MPLSM) in combination with conventional analytical chemistry methods to characterize the tissue distribution of BaP and its principal metabolites in medaka embryos and post-hatch larvae. Embryonic metabolism of BaP was evident by MPLSM prior to liver formation or heart development. A major product of this metabolism was identified by liquid chromatography/mass spectrometry as BaP-3-glucuronide. MPLSM showed that metabolites were sequestered within the yolk, biliary system, and gastrointestinal tract. When the gastrointestinal tract became patent a few days after hatch, the metabolites were rapidly eliminated. These findings indicate that some of the earliest embryonic tissues are metabolically competent and that redistribution of BaP and its metabolic products occurs throughout development. Rapid metabolism of BaP substantially reduces the body burden of parent chemical in the developing embryo, potentially reducing toxicity. It remains unclear whether metabolism of BaP in medaka embryos leads to the formation of DNA adducts associated with genotoxic effects or yields metabolites that later lead to other toxicity in juveniles or adults. Published by Oxford University Press 2007.

Original languageEnglish (US)
Pages (from-to)393-405
Number of pages13
JournalToxicological Sciences
Volume100
Issue number2
DOIs
StatePublished - Dec 2007

Bibliographical note

Funding Information:
The authors thank Rodney Johnson, Kevin Flynn, and Doug Lothenbach for technical advice and assistance, and David Mount and Irv Schultz for critical comments on the manuscript. We also thank Wilson Laboratories, Duluth, MN for assistance with medaka culture, spawning, and egg collection. This project was performed, in part, using compounds provided by the National Cancer Institute’s Chemical Carcinogen Reference Standards Repository operated under contract by Midwest Research Institute, No. N02-CB-07008.

Keywords

  • BaP
  • Embryo
  • Fish
  • Metabolism
  • PAH

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