The ultimate carcinogen of 4-nitroquinoline 1-oxide does

DNA secondary and tertiary structures are known to affect the reaction between the double helix and several damaging agents. We have previously shown that the tertiary structure of DNA Influences the reactivity of 4-acetoxyamlnoquinollne 1-oxide (Ac-4-HAQO), the ultimate carcinogen of 4-nltroqulnoline 1-oxide (4-NQO), being more reactive with naturally supercoiled DNA than with relaxed DNA. The relative proportion of the three main stable adducts and of an unstable adduct, that resulted in strand scission artd/or AP sites, was also affected by the degree of supercolllng of plasmid DNA. In this study we examined the influence of Z-DNA structure on the reactivity of Ac-4-HAQO by mapping the distribution of the two main Ac-4-HAQO adducts, C8-guanlne and N2-guanine, along a (dC-dG)16 sequence inserted at the BamHI site of pBR322 plasmid DNA. This insert adopted the left-handed Z and right-handed B structure depending on the superhellcal density of the plasmid. Sites of C8-guanine adduct formation were determined by hot plperldlne cleavage of Ac-4-HAQO modified DNA, while N2-guanlne adducts were mapped by the arrest of the 3'-5 ' exonuclease activity of T4 DNA polymerase. The results showed that Ac-4-HAQO did not react with guanine residues when the (dC-dG)16 sequence was in Z conformation, while hyperreactivlty at the B- Z junction was ob-served. These results Indicate that Ac-4-HAQO can probe the polymorphism of DNA at the nucleotlde level