benzo[a]pyrene (bap) aimee deconinck. structure and properties polycyclic aromatic hydrocarbon solid...
TRANSCRIPT
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.