Adducts from in vivo action of the carcinogen 4-hydroxyaminoquinoline 1-oxide in rats and from in vitro reaction of 4-acetoxyaminoquinoline 1-oxide with DNA and polynucleotides.
In vivo 4-hydroxyamino[2-3H]quinoline 1-oxide-modified DNA and in vitro 4-acetoxyamino[2-3H]quinoline 1-oxide-modified DNA were enzymatically hydrolyzed, and the hydrolysates were analyzed by high-performance liquid chromatography. The two patterns were compared, and we showed that all of the high-performance liquid chromatography peaks which were recovered from in vivo-modified DNA were present in the hydrolysate of in vitro-modified DNA. Therefore, we used the in vitro 4-acetoxyamino[2-3H]quinoline 1-oxide-modified DNA to investigate the quinoline-purine adducts which are characteristics of the mode of action of the carcinogen 4-nitroquinoline 1-oxide. By comparison with the enzymatic hydrolysates of 4-acetoxyamino[2-3H]quinoline 1-oxide-modified covalent poly(deoxyadenylate-deoxythymidylate) X poly(deoxyadenylate-deoxythymidylate) and covalent poly(deoxyguanylate-deoxycytidylate) X poly(deoxyguanylate-deoxycytidylate) three nitroquinoline adducts were enumerated on the modified DNA. One of them was previously characterized as a C8-guanyl adduct. We proved that the two other are a guanine and an adenine adduct, respectively. A quinoline derivative was identified in the hydrolysates of the in vivo- and in vitro-modified DNAs as 4-aminoquinoline 1-oxide, the origin of which was postulated to be a degradation compound of one (or more) adduct(s). Moreover, the presence of two degradation compounds of the C8-guanyl adduct was shown in mild alkaline conditions. We suspected an imidazole ring-opened form.
D015108:4-Hydroxyaminoquinoline-1-oxide / Q000378:metabolism*; D000634:Aminoquinolines / Q000378:metabolism*; D000818:Animals; D002273:Carcinogens / Q000378:metabolism*; D002645:Chickens; D002851:Chromatography, High Pressure Liquid; D004247:DNA / Q000378:metabolism*; D011067:Poly dA-dT / Q000378:metabolism; D011089:Polydeoxyribonucleotides / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains
D000634:Aminoquinolines; D002273:Carcinogens; D011089:Polydeoxyribonucleotides; D011067:Poly dA-dT; C019530:poly(dC-dG); D015108:4-Hydroxyaminoquinoline-1-oxide; C032982:4-acetoxyaminoquinoline 1-oxide; D004247:DNA