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Daniel J. Albershardt
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  1. Transplacental DNA Adduct Formation by Dibenzo[a,l]pyrene in Mice Daniel J. Albershardt Senior, Dept. of Biochemistry/Biophysics Dr. William M. Baird Laboratory

  2. Overview • Introduction • Methods • Summary

  3. Polycyclic Aromatic Hydrocarbons (PAH) • Found in complex environmental pollutants • Formed by incomplete combustion of organic compounds • Human exposure linked to cancer incidence

  4. Dibenzo[a,l]pyrene Dibenzo[a,l]pyrene (DBP) • Related compounds have been shown to be transplacental Anderson, LM, Ruskie, S, Carter, J, Pittinger, S, Kovatch, RM, Riggs, CW. Pharmacogenetics (1995) 6:364-72

  5. PAH Metabolism • Many sites can be epoxidated. • Epoxides are unstable. • Epoxide hydrolase may hydrolyze the epoxide to a diol. • Subsequent epoxide is a more stable, reactive electrophile.

  6. Chen J, et. al. "MMDB: Entrez's 3D-structure database", Nucleic Acids Res. 2003 Jan; 31(1): 474-7.

  7. Mutations by Dibenzo[a,l]pyrene B. Mahadevan, W.-M. Dashwood, A. Luch, A. Pecaj, J. Doehmer, A. Seidel, C. Pereira, and W. M. Baird. Environ. Mol. Mut.41:131-9 (2003)

  8. Objectives • Determine transplacental DNA adduct formation by DBP in mice • Relevance to human health

  9. Methods 17th Day Gestation 15mg DBP/kg body mass Sacrifice via CO2 (maternal) or decapitation (fetal) Lung and liver removed DNA isolated and 33P postlabeled HPLC Analysis

  10. STANDARD DBP HPLC Profiles Controls:

  11. 6 Hours 1 Day 2 Days 4 Days 6 Days Maternal Lung Tissue HPLC Profiles

  12. Total DNA Adducts (pmol/mg) Total DNA Adducts in Maternal Lung Tissues

  13. Fetal Lung Tissue HPLC Profiles 2 Day Exposure

  14. Total DNA Adducts After 2 Days Exposure Total DNA Adducts (pmol/mg) Maternal P1 P2 P3 P4 P5 P6 P7

  15. Fetal Liver Tissues • No DNA adducts detected using our method

  16. Summary • DNA adducts found in maternal lung tissues at all exposure times • 2 days exposure to DBP formed DNA adducts in fetal lung tissue • No DNA adducts detected in fetal liver tissue after 2 days exposure

  17. Future Research • DNA adduct determination of: • Maternal Liver • Fetal Lung and Liver at Different Exposure Times

  18. Acknowledgements • Dr. William M. Baird • Dr. Kevin Ahern • Dr. Brinda Mahadevan • Tamara Musafia • Howard Hughes Medical Institute • LARC • Dr. David Williams • Yu Zhen • Mandy Louderback