PAHs Flashcards
toxicity of PAHs
major concern is PAH carcinogenicity–becomes bioactivated via CYP450
many PAHs bind to AhR
ya
prototype of PAHs?
Benzo-[a]-pyrene, because it is especially carcinogenic
mechanisms of action of PAHs
- nonpolar narcosis–at high conc, PAHs can cause acute tox due to altered fluidity of cell membranes (like sedatives)
- activation of AhR
- Bioactivation to ultimate carcs–e.g. BAP to 9,10-epoxide by CYP1A1
- bioactivation to quinone structure–>generates ROS
describe nonpolar narcosis
nonspecific, reversible, binding of lipophil structures to lipid membranes–alters fluidity of membrane, which leads to loss of selective permeability of ions (e.g. Na+)
what is the ultimate BaP carc?
7,8-diol-9,10-epoxide–>covalently binds to guanine; causes a GC to AT mutatin (G+BaP binds to A); if this occurs in tumor suppressor p53, can cause tumors–cancer
how do PAHs generate ROS?
bioactivated to quinones via UV rxns or CYP activity;
what can oxidoreductive stress lead to?
DNA ox, lipid ox, protein ox, signalling which leads to apoptosis gene expression–>circles back to redox stress
what is the primary antioxidant defense in our body?
glutathione, GSH
what exogenous antioxs also defend us against ROS?
vit E (alpha-tocopherol) and vitC (ascorbate)–>prevent propagation of lipid peroxides; vit E reduces lipids, and vit C restores vit E to its reduced form