In vitro DNA reaction with an ultimate carcinogen model of 4-nitroquinoline-1-oxide: the 4-acetoxyaminoquinoline-1-oxide. Enzymatic degradation of the modified DNA.
2-3H-Labelled 4-acetoxyaminoquinoline-1-oxide (Ac-4 HAQO), the ultimate carcinogen model of 4-nitroquinoline-1-oxide, was reacted in vitro with native and denatured DNA. We found that Ac-4 HAQO is 2- to 3-fold more reactive than diAc-4 HAQO, another ultimate carcinogen model of 4 NQO which was previously studied [Galiègue et al. (1980) Biochim. Biophys. Acta, 609, 383-391]. Ac-4 HAQO-modified DNA is thermally destabilized: when 1% of the bases of DNA were modified by Ac-4 HAQO, its melting temperature decreased 1.2 degrees C. Enzymatic degradation of Ac-4 HAQO-modified native and denatured DNA's to nucleosides was performed. The hydrolysates were analyzed, first with a simple chromatographic system, and then by h.p.l.c. The compounds recovered from the modified polymers were characterized by h.p.l.c. and a variation in their respective amounts as a function of the secondary structure of DNA was observed. Especially, the N-(deoxyguanosin-(C8-yl)-4-aminoquinoline-1-oxide, the so called dG III adduct, was recovered from DNA, and its amount was evaluated to be approximately 3.5-fold greater in the case of denatured DNA than in the case of native DNA.
D015112:4-Nitroquinoline-1-oxide; D000469:Alkaline Phosphatase / Q000378:metabolism; D000634:Aminoquinolines; D000818:Animals; D002273:Carcinogens; D002417:Cattle; D002645:Chickens; D004247:DNA / Q000378:metabolism*; D003850:Deoxyribonuclease I; D004706:Endodeoxyribonucleases / Q000378:metabolism*; D004912:Erythrocytes; D004926:Escherichia coli / Q000201:enzymology; D007422:Intestines / Q000201:enzymology; D009492:Neurospora crassa / Q000201:enzymology; D009600:Nitroquinolines; D010179:Pancreas / Q000201:enzymology; D010727:Phosphoric Diester Hydrolases / Q000378:metabolism; D012910:Snake Venoms; D013154:Spleen / Q000201:enzymology
D000634:Aminoquinolines; D002273:Carcinogens; D009600:Nitroquinolines; D012910:Snake Venoms; D015112:4-Nitroquinoline-1-oxide; C032982:4-acetoxyaminoquinoline 1-oxide; D004247:DNA; D004706:Endodeoxyribonucleases; D003850:Deoxyribonuclease I; D000469:Alkaline Phosphatase; D010727:Phosphoric Diester Hydrolases