In vitro DNA modification by the ultimate carcinogen of 4-nitroquinoline-1-oxide: influence of superhelicity

摘要: The effect of DNA tertiary structure on in vitro modification by 4-acetoxy-aminoquinoline-1-oxide (Ac-4-HAQO) was investigated. reactivity pAT153 plasmid depended the conformational state molecule: it progressively decreased according to decrease superhelical tension, being negatively supercoiled about two times more susceptible than singly-nicked relaxed DNA. HPLC three main Ac-4-HAQO adducts showed that 3-(deoxyguanosin-N2-yl)-4-aminoquinoline-1-oxide, N-(deoxyguanosin-C8-yl)-4-aminoquinoline-1-oxide and 3-(deoxyadenosin-N6-yl)-4-aminoquinoline-1-oxide accounted for 50, 25 10% total quinoline base all conformations tested, except topoisomers where they 80, 15 5% respectively. resulted also formation apurinic/apyrimidinic sites strand scissions. quantification these damages revealed represent an important fraction damaging events their yield is influenced superstructure. Thus, lesions must be considered as damage induced Ac-4-HAQO.