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

2-³-H-Labelled 4-acetoxyaminoquinoline-1-oxide (Ac-4 HAQO),the ultimate carcinogen model of 4-nitroquinoline-1-oxide, wasreacted in vitro with native and denatured DNA. We found thatAc-4 HAQO is 2- to 3-fold more reactive than diAc-4 HAQO, anotherultimate carcinogen model of 4 NQO which was previously studiedGaliègue 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, itsmelting temperature decreased 1.2°C. Enzymatic degradationof Ac-4 HAQO-modified native and denatured DNA's to nucleosideswas performed. The hydrolysates were analyzed, first with asimple chromatographic system, and then by h.p.l.c. The compoundsrecovered from the modified polymers were characterized by h.p.l.c.and a variation in their respective amounts as a function ofthe secondary structure of DNA was observed. Especially, theN-(deoxyguanosin-(C⁸-yl)-4-aminoquinoline-1-oxide, the so calleddG III adduct, was recovered from DNA, and its amount was evaluatedto be {small tilde} 3.5-fold greater in the case of denaturedDNA than in the case of native DNA.