Scheme 1. Cytochrome P450 Mediated Bioactivation and DNA Reactivity of Standard Chemicals Used for Cigarette Studies^a.

^a(1) Benzo[a]pyrene (B[a]P), metabolized to benzo[a]pyrene-7,8-dihydrodiol-9,10-epoxide that intercalates and covalently binds predominantly with guanine base in DNA, Adapted from information in ref ³³. (2) 4-(Methylnitrosoamino)-1-(3-pyridyl)-1-butanone (NNK) and (3) N-nitrosonicotine (NNN) form hydroxyl forms before binding to nucleobases within DNA. Adapted from information in ref ³⁴.