In vitro DNA reaction with an ultimate carcinogen model of 4-nitro-quinoline-1-oxide: the 4-acetoxyaminoquinoline-1-oxide. Enzymatic degradation of the modified DNA

Abstract

2-3H-labeled 4-acetoxyaminoquinoline-1-oxide (Ac-4 HA-QO), the ultimate carcinogen model of 4-nitroquinoline-1-oxide, was reacted in vitro with native [chicken] and denatured DNA. Ac-4 HAQO is a 2- to 3-fold more reactive than diAc-4 HAQO, another ultimate carcinogen model of 4 NQO which was previously studied. Ac-4 HAQO-modified DNA is thermally destablized: when 1% of the bases of DNA were modified by AC-4 HAQO, its melting temperature decreased 1.2.degree. C. Enzymatic degradation of Ac-4 HAQO-modified native and denatured DNA to nucleosides was performed. The hydrolysates were analyzed, first with a simple chromatographic system, and then by h.p.l.c. [high performance liquid chromatography]. 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. 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 .apprx. 3.5-fold greater in the case of denatured DNA than in the case of native DNA.