In vitro DNA reaction with a carcinogen: the O,O'-diacetyl-4-hydroxyaminoquinoline 1-oxide changes of stability of modified DNA.

The diacetyl derivative of 4-hydroxyaminoquinoline 1-oxide, the proximate carcinogen of 4-nitroquinoline 1-oxide, was reacted in vitro with native and heat denatured chicken erythrocyte DNA under various conditions. The amount of fixed carcinogen was obtained by using the labeled diacetyl derivative and from this result the molar extinction coefficients of bound carcinogen were calculated in order to allow a direct spectrophotometric determination. A decrease in melting temperature of DNA samples modified by O,O'-diacetyl 4-hydroxyaminoquinoline 1-oxide (di Ac-4HAQO) was measured: the melting temperature depression value is equal to 1.4 degrees C per 1% of modified DNA bases. This result was compared with the values previously obtained by Fuchs and coworkers (Fuchs, R. and Daune, M. (1973) FEBS Lett, 34, 295-298 and Fuchs, R. Lefebvre, J.F., Pouyet, J. and Daune, M. (1976) Biochemistry 15, 3347-3351) for N-acetoxy-N-2-acetylaminofluorene-modified DNA and by Lang et al. [25] for the phenanthrylation of the DNA bases of N-acetoxy-N-2-acetylaminophenanthrene-modified DNA.