04_Biochem_physiol_effects_2_S09

04_Biochem_physiol_effects_2_S09 - Bruce Greenberg B2-154...

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Bruce Greenberg B2-154 Ext: 33209 greenber@uwaterloo.ca
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Biochemical and Physiological Effects of Chemicals Part 2 – Organic contaminants 1. Types of effects 2. Negative and positive effects of contaminants on a chemical class basis 3. Modifying factors
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Organics: Many mechanisms of toxicity
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Compounds consisting of fused benzene rings Polycyclic Aromatic Hydrocarbons (PAHs) Anthracene Phenanthrene Fluoranthene Benzo(a)pyrene Properties Low water solubility, lipophillic Relatively unreactive (unless activated) Photoactive
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Should be relatively non-toxic Intact PAHs are somewhat inert Very stable Narcosis possible, but concentration required are very high (mammals 100 mg/kg in food) Metabolized, so they do not biomagnify However, they can undergo photochemical and biological activation to form biologically damaging compounds PAH Toxicity – Negative effects
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Photochemical activation PAHs absorb solar UV radiation Simultaneous exposure of the organism and PAHs to UV - Photosensitization Pre-exposure of PAHs to UV PAH photoxidation (oxyPAHs) oxyPAH toxicity - Photomodification Toxicity at ~ 10 μ g/L Biochemical activation Enzymatic transformation of PAHs (hydroxylation) Organism can excrete more soluble PAH But oxyPAH more reactive (cytotoxic/genotoxic) Endocrine disruption Some oxyPAHs mimic hormones PAHs induce cytochrome P450 (which can also degrade steroid hormones) PAH Activation
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Phototoxic PAHs: Anthracene, Fluoranthene, Benzo(a)pyrene, Phenanthrene and many others Two mechanisms: Photosensitization and Photooxidation PAH photoinduced toxicity (P. 124, 200) h ν PAH 1 PAH* Oxidation from singlet-state Photomodification 3 PAH* Photosensitization 2 TISSUE DAMAGE O 2 Oxidation from triplet-state O 2 Toxic PAH quinones + other products
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Photosensitization – PAH must be in the organism. Impact greatest on organisms transparent to UV Serine in a protein (or other hydroxy) R 2 CHOH + 1 O 2 R 2 C-O-H OO-H R 2 C=O + H 2 O 2 Photooxidation – Can occur inside or outside the organism O O O O OH OH h ν , O 2 h ν , O 2 Anthroquinone is a redox cycler 1,2-dihydroxy-anthroquinone inhibits photosynthesis and respiration oxyPAHs are mutagenic
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Impacts on respiration NADH DHase Cyt c Oxidase Cyt bc NADH UQ UQH 2 Cyt b Fe-S Cyt c1 ATQ Redox Cycling Cyt c Cyt a-Cu FMN O 2 O 2 H 2 O 2 OH . Fe-S Cyt a3-Cu O 2 H 2 O 1,2-dhATQ Inhibition
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Some PAHs are pro-carcinogens. They become carcinogenic after oxidation Biochemical activation of PAHs (P. 114, 139) 7,12-dimethyl-benzanthracene Benzo(a)pyrene Two enzymatic activities Cytochrome P450 and epoxide hydroxylase Most metabolites glutathione-linked or glycosylated and eliminated A subset (e.g. Diol epoxides) carcinogenic OH HO O
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Rainbow trout – 0.1 μ g/L BAP – 36 d – Abnormal Cells Sea urchins – 0.5 μ g/L BAP – Teratogenesis Trout – Injected with Hamilton Harbor sediment – BAP like tumors Sydney Harbor, NS – Lower diversity and abundance –
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04_Biochem_physiol_effects_2_S09 - Bruce Greenberg B2-154...

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