O

1
Major metabolites of benzoapyrene by MFO system
1,6-Q
1-OH
1
12
11
2
10
3
9
8
4
7
5
6
benzo
a
pyrene
6,12-Q
6-OH
O
O
3,6-Q
3-OH
7-OH, 9-OH, 12-OH and the 4,5-Q have also been
reported
H
O
H
H
O
H
H
O
H
diolepoxide
2
Arene oxide ? phenol rearrangement
3
Stereochemistry of hydration by epoxide hydrolase
H2O
4
BP diolepoxide stereo isomers
()-anti 7R,8S,9S,10R-BPDE
5
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6
Adducts of anti-BPDE with exocyclic amino groups
of nucleobases
Heavy lines show the aromatic p-system conjugated
with, and stabilizing the incipient positive
charge resulting from attack at epoxide ring.
This situation favors addition adjacent to
aromatic ring.
7
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8
()-trans-anti--BPDEN2-dGuo adduct at
primer-template junction
5'
9
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10
Oxidized angular ring
Distal end of pyrene system
11
adduct of (-)-trans-anti-BPDE with N6-dAdo
opposite dThyd from N-Ras fragment
5? face of dAdo
Looking down helix axis
Looking perpendicular to helix axis
12
cis adduct of ()-anti-BPDE at N6 of dAdo
5? face of dAdo
13
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14
()-trans-anti-benzogchrysenedAdo
Inset benzogchrysene skeleton
15
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16
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17
BAY REGION THEORY
If a PAH has a bay region and shows genotoxic
activity, the ultimate active metabolite will be
the bay region diolepoxide.
18
Aflatoxin B1 activation
human CYP3A4
19
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20
Reactions of AFB1-dGuo adduct
hydrolysis
depurination
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22
Vinyl chloride activation
23

24
ACTIVATION OF DIMETHYLNITROSAMINE
GENERAL STRUCTURE
monomethyl nitrosamine
azotic acid
25
Activation of 2-AAF (general for amines)
other amines of commercial importance
26
Nitrenium ion adducts
C8 adduct of AAF
C1 adduct of AAF
C8 adduct 1-aminopyrene
27
Other important environmental nitro-PAH
Activation of nitroaromatics-multiple pathways,
MFO and nitroreductase
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29
Deamination by bisulfite reaction
30
Direct acting mutagens