DNA Strand Scission and Apurinic Sites Induced by Photoactivated Aflatoxins1

Covalent binding of photoactivated aflatoxins to DNA in vitro under close-to-physiological conditions resulted in the formation of apurinic sites and in strand scission. Linearized pBR322 DNA was randomly fragmented, and supercoiled DNA was relaxed during the binding reac tion. A primary amine facilitated fragmentation and relaxation. Quanti tative measurements of relaxation revealed that the probability of a binding event to be converted into a DNA chain break was approximately 3-5% in the absence of a primary amine. The presence of the latter increased the probability approximately 2to 3-fold. The results are compatible with the model that photoactivated aflatoxins bind to guanines on DNA; some of these guanine adducts are released, creating apurinic sites. The latter are converted into DNA chain breaks at physiological pH and temperature. Thus, apurinic sites and DNA chain breaks must be considered as quantitatively important (genotoxic) DNA damage in duced by aflatoxins.