PAHs

Question 1

toxicity of PAHs

Answer 1

major concern is PAH carcinogenicity–becomes bioactivated via CYP450

Question 2

many PAHs bind to AhR

Answer 2

ya

Question 3

prototype of PAHs?

Answer 3

Benzo-[a]-pyrene, because it is especially carcinogenic

Question 4

mechanisms of action of PAHs

Answer 4

1. nonpolar narcosis–at high conc, PAHs can cause acute tox due to altered fluidity of cell membranes (like sedatives)
2. activation of AhR
3. Bioactivation to ultimate carcs–e.g. BAP to 9,10-epoxide by CYP1A1
4. bioactivation to quinone structure–>generates ROS

Question 5

describe nonpolar narcosis

Answer 5

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+)

Question 6

what is the ultimate BaP carc?

Answer 6

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

Question 7

how do PAHs generate ROS?

Answer 7

bioactivated to quinones via UV rxns or CYP activity;

Question 8

what can oxidoreductive stress lead to?

Answer 8

DNA ox, lipid ox, protein ox, signalling which leads to apoptosis gene expression–>circles back to redox stress

Question 9

what is the primary antioxidant defense in our body?

Answer 9

glutathione, GSH

Question 10

what exogenous antioxs also defend us against ROS?

Answer 10

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