Benzo[a]pyrene(BaP)

Aimee Deconinck

Structure and Properties

Polycyclic aromatic hydrocarbonSolid pale yellow crystal platesMolecular Mass 252.31 g/molMP 179˚C BP 495˚CDensity 1.351 g/mlOctanol-Water Partition Coefficient 6.06Vapor Pressure 5.6 x 10e-9 mm Hg

Production History

Formed from incomplete combustion of organic materials

No known commercial use Employed in carcinogenesis research

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

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

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

Mode of Entry into Organisms

Absorbed through skin, gills Ingested

Particulates in water Prey containing BaP

Lipid-soluble

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

Biochemical Metabolism and Breakdown

Cyp1 adds epoxide Benzo(a)pyrene hydroxylase adds trans

hydroxyl groups to BaP

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

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

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

Bibliography ChemInfo http://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.