1. Benzo[a]pyrene (BaP) Aimee Deconinck

2. Structure and Properties Polycyclic aromatic hydrocarbon Solid pale yellow crystal plates Molecular Mass 252.31 g/mol MP 179˚CBP 495˚C Density 1.351 g/ml Octanol-Water Partition Coefficient 6.06 Vapor Pressure 5.6 x 10e-9 mm Hg

3. Production History Formed from incomplete combustion of organic materials No known commercial use Employed in carcinogenesis research

4. Entry into Aquatic Systems Most BaP originates from non-point sources Result of industrial processes, transportation, food preparation, wildfires, etc. Adsorbs to particulates in air which ultimately dissolve in water

5. Chemical Reactivity Destroyed by photooxidation in the atmosphere Also degraded by Stropharia coronilla (litter- decomposing bacteria) in presence of Mn Not spontaneously reactive, but can react with organic reagents (oxidizers and strong acids) In powder form, can be ignited by static charge

6. Toxicity to Aquatic Life Once believed BaP did not show acute toxicity within its solubility limits Recent studies show that it can be significantly more toxic under UV light Studies of larval stages of several marine animals showed malformed development Bioaccumulates

7. Mode of Entry into Organisms Absorbed through skin, gills Ingested Particulates in water Prey containing BaP Lipid-soluble

8. Noted Toxic Effects Carcinogenic, mutagenic, teratogenic, immunotoxic, and reproductively toxic Less noticeable effects from acute exposure, but significant effects from chronic exposure System wide effects; affects multiple organs Induces expression of phase I and phase II enzymes

9. Biochemical Metabolism and Breakdown Cyp1 adds epoxide Benzo(a)pyrene hydroxylase adds trans hydroxyl groups to BaP

10. Molecular Mode of Interaction The oxidized BaP binds to guanine residues in DNA, intercalating the minor groove Inhibits normal DNA topoisomerase 1 (top 1) binding

11. Molecular Mode of Interaction Top1 relaxes DNA supercoiling, relieves torsional strian during DNA processing, and re-ligates DNA BaP-guanine adduct induces top 1 to generate new cleavage sites in the DNA while suppressing normal cleavage sites Bap-guanine adduct also reduces binding and methylating efficiencies of methyltransferases

12. Detoxification and Defense Strategies of Organism Glutathione S-transferases (GST) conjugate with the oxidized BaP during phase II Rate of this reaction determines toxicity of BaP In mammals, BaP-GST adduct is transported out of the cell via antiporters in phase III and expelled through excrement

13. Bibliography ChemInfo http://www.intox.org/databank/documents/chemical/benzopyr/cie698.htmhttp://www.intox.org/databank/documents/chemical/benzopyr/cie698.htm B.P. Lyons, C.K. Pascoe, I.R.B. McFadzen. “Phototoxicity of pyrene and benzo[a]pyrene to embryo-larval stages of the pacific oyster Crassostrea gigas.” Marine Environmental Research. 54 (2002) 627–63. D.R. Livingstone. “The fate of organic xenobiotics in aquatic ecosystems: quantitative and qualitative differences in biotransformation by invertebrates and fish.” Comparative Biochemistry and Physiology Part A 120 (1998) 43–49. Yves Pommier, Glenda Kohlhagen, Philippe Pourquier, Jane M. Sayer, Heiko Kroth, and Donald M. Jerina. “Benzo[a]pyrene diol epoxide adducts in DNA are potent suppressors of a normal topoisomerase I cleavage site and powerful inducers of other topoisomerase I cleavages.” Proceedings of the National Academy of Sciences 97 (2000) 2040-2045. M. Banni, Z. Bouraoui, J. Ghedira, C. Clerandeau, H. Guerbej, J. F. Narbonne and H. Boussetta. “Acute effects of benzo[a]pyrene on liver phase I and II enzymes, and DNA damage on sea bream Sparus aurata.” Fish Physiology. DOI 10.1007/s10695-008-9210-9 Mary E.Kushman, Sandra L.Kabler, Melissa H.Fleming, Srivani Ravoori, Ramesh C.Gupta, Johannes Doehmer, Charles S.Morrow and Alan J.Townsend. “Expression of human glutathione S-transferase P1 confers resistance to benzo[a]pyrene or benzo[a]pyrene-7,8- dihydrodiol mutagenesis, macromolecular alkylation and formation of stable N2-Gua-BPDE adducts in stably transfected V79MZ cells co-expressing hCYP1A1.” Carcinogenesis 28 (2007) 207-214.