Changes of stability and conformation of DNA following the covalent binding of a carcinogen

Recently Miller [ 1 ] has thrown some light on the effects of many carcinogenic chemicals. He has shown that the activity of these compounds or their metabolic derivatives is related to their strong electrophilic reactivity. The active form of those carcinogens is covalently bound to nucleic acids and proteins in induced tumors [ 11. In the case of acetylaminofluorene (AAF) Miller et al. [2] have shown that the last metabolic derivative was an ester of N-hydroxy-AAF. We have therefore studied the effects of N-acetoxy-AAF (NAcO-AAF) on native DNA. The analysis of melting profiles of modified DNA gives evidence for a destabilizing effect which is interpreted as the opening of G-C base pairs. Furthermore it is likely that the carcinogen reacts preferentially with G-C rich regions.