MFO

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ACTIVATION OF 2-AAF
glucuronide, excretion
MFO
N-hydroxylation
hydroxylamine
acyl
sulfotransferase
transferase
MFO
C-hydroxylation
R H, CH3CO-
nitrenium transient
glucuronidation, excretion
covalent DNA binding,
mutagenesis, carcinogenesis
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ADDUCT FORMATION
transition state for opening of bay region epoxide
heavy lines indicate the
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ORIENTATION OF ()-trans-anti-DIOLEPOXIDE ADDUCTS
OF BP AT Gua N2
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Adduct of (-)-trans-anti-BPDE with N6-dAdo
opposite dThyd
axis
5? face of dAdo
Looking down helix axis
sequence of modified DNA 5' -GCTC(A)CGAG-3' 3'
-CGAT T GCTC-5'
Looking perpendicular to helix axis
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AFB1-dGuo Adduct Opposite dCyd
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Reactions of AFB1-dGuo adduct
O
O
O
O
C
H
3
H
O
hydrolysis
H
H
O
H
O
O
O
O
depurination
O
O
C
H
3
formamidopyrimidine (Fapy)
H
O
H
H
O
O
O
N
H
N
N
N
H
N
2
apurinic site
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Ring-opened formamido pyrimidine (Fapy) of AFB1
adduct at dGuo N7
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ADDUCT OF 2-CHLOROOXIRANE WITH dGuo AND OTHER
dNUCLEOSIDES
? etheno
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3,N4-Etheno-dC opposite dGuo adduct
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FORMATION OF 2-AAF ADDUCT
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Common direct acting alkylating agents
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REACTIVE ALDEHYDES FROM LIPID PEROXIDATION AND
TRICYCLIC ADDUCTS
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Oxidation of 8-oxodGuo by singlet oxygen (1O2)