1. O O 1 2 3 4 5 6 7 8 9 10 11 12 benzo[a]pyrene 1-OH 6-OH 3-OH* 1,6-Q 6,12-Q 3,6-Q OH H H HO O H H diolepoxide Major metabolites of benzo[a]pyrene by MFO system 7-OH, 9-OH, 12-OH and the 4,5-Q have also been reported

2. Arene oxide  phenol rearrangement

3. Stereochemistry of hydration by epoxide hydrolase H2OH2O

4. BP diolepoxide stereo isomers (+)-anti: 7R,8S,9S,10R-BPDE

6. Adducts of anti-BPDE with exocyclic amino groups of nucleobases Heavy lines show the aromatic π-system conjugated with, and stabilizing the incipient positive charge resulting from attack at epoxide ring. This situation favors addition adjacent to aromatic ring.

8. 5' (+)-trans-anti--BPDE:N 2 -dGuo adduct at primer-template junction

10. Oxidized angular ring Distal end of pyrene system

11. adduct of (-)-trans-anti-BPDE with N 6 -dAdo: opposite dThyd from N-Ras fragment Looking down helix axis Looking perpendicular to helix axis 5 face of dAdo

12. cis adduct of (+)-anti-BPDE at N 6 of dAdo 5 face of dAdo

13. (-)-trans-anti-5-methylchrysene:dGuo adduct at the hindered bay region 5' 3'

14. (+)-trans-anti-benzo[g]chrysene:dAdo Inset: benzo[g]chrysene skeleton

15. R,S-trans-anti-benzo[c]phenanthrene:dGuo SR

16. classical intercalation 5-insertion S-trans-anti-B[c]Ph 1(S) 5…C[G*]C… normal duplex classical intercalation 3-insertion R-trans-anti-B[c]Ph 1(R) 5…C[G*]C… normal duplex

17. BAY REGION THEORY O  transition state for opening of bay region epoxide heavy lines indicate the aromatic  aromatic system  Nu If a PAH has a bay region and shows genotoxic activity, the ultimate active metabolite will be the bay region diolepoxide.

18. Aflatoxin B 1 activation human CYP3A4

19. Albumin lysine

20. Reactions of AFB 1 -dGuo adduct depurination hydrolysis

21. AFB 1 -FAPy dGuo adduct N7 N9

22. Vinyl chloride activation

23. +

24. ACTIVATION OF DIMETHYLNITROSAMINE GENERAL STRUCTURE azotic acid monomethyl nitrosamine

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. Activation of nitroaromatics-multiple pathways, MFO and nitroreductase Other important environmental nitro- PAH

28. Deamination via diazotization reaction

29. Deamination by bisulfite reaction

30. Direct acting mutagens