The reaction of acetyl-4-hydroxyaminoquinoline 1-oxide with DNA: quantitation of single-strand break formation and hyper-reactivity of DNA termini.
Monoacetyl-hydroxyaminoquinoline 1-oxide (Ac-HAQO) is a model of the ultimate form of the carcinogen 4-nitroquinoline 1-oxide and so it is useful to characterize its reactions with DNA. We find that Ac-HAQO produces one single-strand break (SSB) for every 60 adducts formed in a reaction with supercoiled DNA. The SSBs do not appear to be formed by a free radical reaction and they are distributed throughout the DNA molecule without regard to nucleotide specificity. Unique DNA fragments were reacted with Ac-HAQO. These substrates could not be degraded by the 3'-5' exonuclease action of T4 DNA polymerase unless they were first cleaved by a restriction endonuclease. This indicated that the ends of all the DNA molecules were blocked by adduct formation in spite of the low overall frequency of adducts per DNA molecule.
Panigrahi
G B
GB
Department of Biochemistry, University of Western Ontario, London, Canada.
Walker
I G
IG
D000634:Aminoquinolines / Q000378:metabolism*; D001483:Base Sequence; D002273:Carcinogens / Q000378:metabolism*; D004249:DNA Damage; D004277:DNA, Single-Stranded / Q000378:metabolism*; D004259:DNA-Directed DNA Polymerase / Q000494:pharmacology; D005092:Exonucleases / Q000494:pharmacology; D008969:Molecular Sequence Data
D000634:Aminoquinolines; D002273:Carcinogens; D004277:DNA, Single-Stranded; C032982:4-acetoxyaminoquinoline 1-oxide; D004259:DNA-Directed DNA Polymerase; D005092:Exonucleases