1. ACTIVATION OF 2-AAF glucuronidation, excretion glucuronide, excretionH 2 N O 3 S - R +
MFO
N-hydroxylation
hydroxylamine
acyl
transferase
sulfotransferase
MFO
C-hydroxylation
R= H, CH3CO-
nitrenium transient
glucuronidation, excretion
covalent DNA binding,
mutagenesis, carcinogenesis

3. RELATION BETWEEN DNA DAMAGE AND MUTATION
DNA +activated compound
lesion
processing/repair
no effect
mutation
RELATION BETWEEN DNA DAMAGE AND MUTATION

4. ADDUCT FORMATION O d Nu
transition state for opening of bay region epoxide
heavy lines indicate the p-
aromatic system

5. ORIENTATION OF (±)-trans-anti-DIOLEPOXIDE ADDUCTS OF BP AT Gua N2

6. 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

7. AFB1-dGuo Adduct Opposite dCyd

8. Reactions of AFB1-dGuo adductH 3 H O
hydrolysis H H O H O O O O O O C H
depurination 3
formamidopyrimidine
(Fapy) H O H O H O N O H N H N N N 2 O P H
apurinic site

9. Ring-opened formamido pyrimidine (Fapy) of AFB1 adduct at dGuo N7
DEOXYRIBONUCLEIC ACID MAY HM1
TITLE THE SOLUTION NMR STRUCTURE OF A THERMALLY STABLE FAPY ADDUCT
TITLE 2 OF AFLATOXIN B1 IN AN OLIGODEOXYNUCLEOTIDE DUPLEX REFINED
TITLE 3 FROM DISTANCE RESTRAINED MOLECULAR DYNAMICS SIMULATED
TITLE 4 ANNEALING, MINIMIZED AVERAGE STRUCTURE
COMPND MOL_ID: 1;
COMPND 2 MOLECULE: FAPY ADDUCT OF AFLATOXIN B1 MODIFIED DNA DUPLEX;
COMPND 3 CHAIN: A, B;
COMPND 4 ENGINEERED: YES;
COMPND 5 OTHER_DETAILS: CHAIN A, GUA 5 -> FAG, FAPY ADDUCT OF
COMPND 6 AFLATOXIN B1\: 2'-DEOXY-N7-(8,9-DIHYDRO)-8-
COMPND 7 (2,6-DIAMINO-4-OXO-3,4-DIHYDROPYRIMIDYL-5-FORMAMIDO-9-
COMPND 8 (HYDROXY-AFLATOXIN B1)-GUANOSINE
SOURCE MOL_ID: 1;
SOURCE 2 SYNTHETIC: YES
KEYWDS AFLATOXIN B1, FAPY, FORMAMIDOPYRIMIDINE, INTERCALATION, DNA
KEYWDS 2 DUPLEX, NMR, SOLUTION STRUCTURE, DNA ADDUCT,
KEYWDS 3 DEOXYRIBONUCLEIC ACID
EXPDTA NMR, MINIMIZED AVERAGE STRUCTURE
AUTHOR H.MAO,Z.DENG,F.WANG,T.M.HARRIS,M.P.STONE
REVDAT OCT-98 1HM1 0
JRNL AUTH H.MAO,Z.DENG,F.WANG,T.M.HARRIS,M.P.STONE
JRNL TITL AN INTERCALATED AND THERMALLY STABLE FAPY ADDUCT OF
JRNL TITL 2 AFLATOXIN B1 IN A DNA DUPLEX: STRUCTURAL REFINEMENT
JRNL TITL 3 FROM 1H NMR
JRNL REF BIOCHEMISTRY V
Ring-opened formamido pyrimidine (Fapy) of AFB1 adduct at dGuo N7

10. ADDUCT OF 2-CHLOROOXIRANE WITH dGuo AND OTHER dNUCLEOSIDES
 = “etheno”

11. 3,N4-Etheno-dC opposite dGuo adduct
DEOXYRIBONUCLEIC ACID JAN B6X
TITLE 3,N4-ETHENO-2'-DEOXYCYTIDINE OPPOSITE GUANINE IN AN 11-MER
TITLE 2 DUPLEX, SOLUTION STRUCTURE FROM NMR AND MOLECULAR DYNAMICS,
TITLE STRUCTURES
COMPND MOL_ID: 1;
COMPND 2 MOLECULE: 11-MER DNA DUPLEX;
COMPND 3 CHAIN: A, B;
COMPND 4 ENGINEERED: YES
SOURCE MOL_ID: 1;
SOURCE 2 SYNTHETIC: NON-BIOLOGICAL SEQUENCE
KEYWDS DEOXYRIBONUCLEIC ACID, ETHENODC, EDC, EXOCYCLIC LESION
EXPDTA NMR, 4 STRUCTURES
AUTHOR D.CULLINAN,F.JOHNSON,A.P.GROLLMAN,M.EISENBERG,
AUTHOR 2 C.DE LOS SANTOS
REVDAT APR-99 1B6XA 3
3,N4-Etheno-dC opposite dGuo adduct

12. FORMATION OF 2-AAF ADDUCT

13. 2-AF-dGuo adduct at template junction
DEOXYRIBONUCLEIC ACID JUL C0Y
TITLE SOLUTION STRUCTURE OF THE [AF]-C8-DG ADDUCT POSITIONED
TITLE 2 OPPOSITE DA AT A TEMPLATE-PRIMER JUNCTION
COMPND MOL_ID: 1;
COMPND 2 MOLECULE: DNA (5'-D(*AP*AP*CP*GP*CP*TP*AP*CP*CP*AP*TP*CP*C)
COMPND ');
COMPND 4 CHAIN: A;
COMPND 5 ENGINEERED: YES;
COMPND 6 BIOLOGICAL_UNIT: MONOMER;
COMPND 7 OTHER_DETAILS: N ATOM OF AF-GROUP LINKED TO C8 ATOM OF G 4;
COMPND 8 MOL_ID: 2;
COMPND 9 MOLECULE: DNA (5'-D(*GP*GP*AP*TP*GP*GP*TP*AP*GP*C)-3');
COMPND 10 CHAIN: B;
COMPND 11 ENGINEERED: YES;
COMPND 12 BIOLOGICAL_UNIT: MONOMER
SOURCE MOL_ID: 1;
SOURCE 2 SYNTHETIC: YES;
SOURCE 3 MOL_ID: 2;
SOURCE 4 SYNTHETIC: YES
KEYWDS DNA DUPLEX, AMINOFLUORENE ADDUCT, CARCINOGEN ADDUCT,
KEYWDS 2 TEMPLATE-PRIMER JUNCTION, DEOXYRIBONUCLEIC ACID
EXPDTA NMR, 6 STRUCTURES
AUTHOR Z.GU,A.GORIN,B.E.HINGERTY,S.BROYDE,D.J.PATEL
REVDAT AUG-99 1C0Y 0
JRNL AUTH Z.GU,A.GORIN,B.E.HINGERTY,S.BROYDE,D.J.PATEL
JRNL TITL SOLUTION STRUCTURES OF THE [AF]-C8-DG ADDUCT
JRNL TITL 2 POSITIONED OPPOSITE DA AT A TEMPLATE-PRIMER
JRNL TITL 3 JUNCTION
JRNL REF BIOCHEMISTRY V

14. Common direct acting alkylating agents

15. deamination of nucleosides

16. REACTIVE ALDEHYDES FROM LIPID PEROXIDATION AND TRICYCLIC ADDUCTS
malondialdehyde
(enol form) N d R
1,N 2
-propeno dG
(M1G)
acrolein C 3
crotonaldehyde
4-hydroxy-2-nonenal
4 isomers
4-hydroxy-2,3-epoxynonanal
-etheno dG +
-propano dG, two isomers

17. PRODUCTS OF ATTACK OF HYDROXYL RADICAL ON NUCLEOBASES2 O d R
5-hydroxy dCyd
5,6-dihydroxy-5,6-dihydro
dCyd C 3
dThyd glycol
PRODUCTS OF ATTACK OF HYDROXYL RADICAL ON NUCLEOBASES , r e u c t i o n - Z I z F a p y G 8 x

18. PRODUCTS OF 4' AND 5',5'' DEOXYRIBOSE HYDROGEN ABSTRACTION
phosphoglycolate
base propenal
nucleotide 5'-aldehyde
furfural
aerobic
anaerobic
both R O 3 P H C '
PRODUCTS OF 4' AND 5',5'' DEOXYRIBOSE HYDROGEN ABSTRACTION
R, R'= DNA strand - B 4'
5',5''

19. Oxidation of 8-oxodGuo by singlet oxygen (1O2)