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 degrees +/- 1.5 degrees for negatively supercoiled topoisomers and -6.5 degrees +/- 1.4 degrees 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.
Fronza
G
G
Instituto Nazionale per la Ricerca sul Cancro, Genova, Italy.
Tornaletti
S
S
Menichini
P
P
Galiègue-Zouitina
S
S
Bailleul
B
B
Loucheux-Lefebvre
M H
MH
Abbondandolo
A
A
Pedrini
A M
AM
D000634:Aminoquinolines / Q000737:chemistry*; D001080:Apurinic Acid / Q000737:chemistry; D004249:DNA Damage; D004278:DNA, Superhelical / Q000737:chemistry; D004587:Electrophoresis, Agar Gel; D066298:In Vitro Techniques; D009690:Nucleic Acid Conformation; D010957:Plasmids
D000634:Aminoquinolines; D004278:DNA, Superhelical; D001080:Apurinic Acid; C032982:4-acetoxyaminoquinoline 1-oxide