Bond breaks of nucleotides by dissociative electron transfer of nonequilibrium prehydrated electrons: a new molecular mechanism for reductive DNA damage.
DNA damage is a central mechanism in the pathogenesis and treatment of human diseases, notably cancer. Little is known about reductive DNA damage in causing genetic mutations during oncogenesis and killing cancer cells during radiotherapy. The prehydrated electron (e(-)(pre)) has the highest yield among all the radicals generated in cells during ionizing radiation and has subpicosecond lifetimes (10(-13) s) and energies below 0 eV, but its role in DNA damage is unknown. In this work, our real-time measurements by femtosecond time-resolved laser spectroscopy have revealed that while adenine and cytosine can effectively trap an e(-)(pre) to form stable anions, thymidine and especially guanine are highly susceptible to dissociative electron transfer of e(-)(pre), leading to bond dissociation in DNA. Our finding demonstrates a dissociative electron transfer pathway for reductive DNA damage that might be related to various diseases such as cancer and stroke. Moreover, this finding challenges the conventional notion that damage to the genome is mainly induced by the oxidizing OH* radical and might eventually lead to improved radiotherapy of cancer and radioprotection of humans.
Wang
Chun-Rong
CR
Department of Physics and Astronomy, University of Waterloo, 200 University Avenue West, Waterloo, Ontario N2L 3G1, Canada.
Nguyen
Jenny
J
Lu
Qing-Bin
QB
D000225:Adenine / Q000737:chemistry; D003596:Cytosine / Q000737:chemistry; D004247:DNA / Q000737:chemistry*; D004249:DNA Damage; D004583:Electrons; D006147:Guanine / Q000737:chemistry; D009711:Nucleotides / Q000737:chemistry*; D010084:Oxidation-Reduction; D011839:Radiation, Ionizing; D013057:Spectrum Analysis; D013936:Thymidine / Q000737:chemistry; D014867:Water / Q000737:chemistry
D009711:Nucleotides; D014867:Water; D006147:Guanine; D003596:Cytosine; D004247:DNA; D000225:Adenine; D013936:Thymidine