DNA strand scission and apurinic sites induced by photoactivated aflatoxins.
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 reaction. A primary amine facilitated fragmentation and relaxation. Quantitative 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 2- to 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 induced by aflatoxins.
D016604:Aflatoxin B1; D000348:Aflatoxins / Q000378:metabolism / Q000494:pharmacology* / Q000528:radiation effects; D001080:Apurinic Acid / Q000528:radiation effects*; D004247:DNA / Q000378:metabolism / Q000528:radiation effects*; D004249:DNA Damage; D007700:Kinetics; D010957:Plasmids; D011119:Polynucleotides / Q000528:radiation effects*; D014466:Ultraviolet Rays
D000348:Aflatoxins; D011119:Polynucleotides; D001080:Apurinic Acid; C029753:aflatoxin B2; D004247:DNA; D016604:Aflatoxin B1