EXTENT OF HELIX PERTURBATION ASSOCIATED WITH DNA MODIFICATION BY THE O-ACETYL DERIVATIVE OF THE CARCINOGEN 4-HYDROXYAMINOQUINOLINE-1-OXIDE

Duplex unwinding associated with DNA modification by 4-acetoxyaminoquinoline-1-oxide, a model ultimate carcinogen of 4-nitroquinoline-1-oxide, has been determined by the agarose gel electrophoresis band-shift method. An average unwinding angle per stable adduct of -15.1° ± 1.5° for negatively spercoiled topoisomers and -6.5° ± 1.4° for positively supercoiled topoisomers was obtained. Because of the different proportion of stable adducts (dGuo-N2-AQO, dGuo-C8-AQO, dAdo-N6-AQO) between negatively (8:1.5:0.5) and positively (5:2.5:1) supercoiled topoisomers, the difference in unwinding angles is suggestive of a diverse contribution of the various adducts to the overall conformational change. Since the largest unwinding angle was coupled with the highest proportion of dGuo-N2-AQO adduct, it is likely that this adduct is the most distortive lesion. A contribution of sites of base loss to DNA unwinding was also observed. © 1990.