Q.-B. Lu

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.

Direct observation of ultrafast-electron-transfer reactions unravels high effectiveness of reductive DNA damage

Both water and electron-transfer reactions play important roles in chemistry, physics, biology, and the environment. Oxidative DNA damage is a well-known mechanism, whereas the relative role of reductive DNA damage is unknown. The prehydrated electron (), a novel species of electrons in water, is a fascinating species due to its fundamental importance in chemistry, biology, and the environment. is an ideal agent to observe reductive DNA damage. Here, we report both the first in situ femtosecond time-resolved laser spectroscopy measurements of ultrafast-electron-transfer (UET) reactions of with various scavengers (KNO3, isopropanol, and dimethyl sulfoxide) and the first gel electrophoresis measurements of DNA strand breaks induced by and OH• radicals co-produced by two-UV-photon photolysis of water. We strikingly found that the yield of reductive DNA strand breaks induced by each is twice the yield of oxidative DNA strand breaks induced by each OH• radical. Our results not only unravel the long-standing mystery about the relative role of radicals in inducing DNA damage under ionizing radiation, but also challenge the conventional notion that oxidative damage is the main pathway for DNA damage. The results also show the potential of femtomedicine as a new transdisciplinary frontier and the broad significance of UET reactions of in many processes in chemistry, physics, biology, and the environment.

Spectroscopic characterization of carbon chains in nanostructured tetrahedral carbon films synthesized by femtosecond pulsed laser deposition

A comparative study of carbon bonding states and Raman spectra is reported for amorphous diamondlike carbon films deposited using 120 fs and 30 ns pulsed laser ablation of graphite. The presence of sp(1) chains in femtosecond carbon films is confirmed by the appearance of a broad excitation band at 2000-2200 cm(-1) in UV-Raman spectra. Analysis of Raman spectra indicates that the concentrations of sp(1)-, sp(2)-, and sp(3)-bonded carbon are approximately 6%, approximately 43%, and approximately 51%, respectively, in carbon films prepared by femtosecond laser ablation. Using surface enhanced Raman spectroscopy, specific vibrational frequencies associated with polycumulene, polyyne, and trans-polyacetylene chains have been identified. The present study provides further insight into the composition and structure of tetrahedral carbon films containing both sp(2) clusters and sp(1) chains.

Giant enhancement of electron-induced dissociation of chlorofluorocarbons coadsorbed with water or ammonia ices: Implications for atmospheric ozone depletion

The Cl− yield produced by dissociative electron attachment of a submonolayer of CF2Cl2 is enhanced by factors of 102 and 104 when CF2Cl2 is coadsorbed with water ice and ammonia ice, respectively, on a surface at ∼25 K. Moreover, the magnitude of Cl− enhancement increases strongly with decreasing CF2Cl2 concentration. This enhancement is attributed to dissociation of CF2Cl2 by capture of electrons self-trapped in polar water or ammonia molecules. This process may be an unrecognized sink for chlorofluorocarbons in the atmosphere. Cl− ions produced may be directly or indirectly converted to Cl atoms, which then destroy ozone.

Antioxidant Induces DNA Damage, Cell Death and Mutagenicity in Human Lung and Skin Normal Cells

Clinical trials have shown that antioxidant supplementation increased the risk of lung and skin cancers, but the underlying molecular mechanism is unknown. Here, we show that epigallocatechin gallate (EGCG) as an exemplary antioxidant induced significant death and DNA damage in human lung and skin normal cells through a reductive mechanism. Our results show direct evidence of reductive DNA damage in the cells. We found that EGCG was much more toxic against normal cells than H₂O₂ and cisplatin as toxic and cancer-causing agents, while EGCG at low concentrations (≤100 μM) increased slightly the lung cancer cell viability. EGCG induced DNA double-strand breaks and apoptosis in normal cells and enhanced the mutation frequency. These results provide a compelling explanation for the clinical results and unravel a new reductive damaging mechanism in cellular processes. This study therefore provides a fresh understanding of aging and diseases, and may lead to effective prevention and therapies.

Enhancements in dissociative electron attachment to CF4, chlorofluorocarbons and hydrochlorofluorocarbons adsorbed on H2O ice

We report that the absolute cross sections for dissociative attachment of approximately 0 eV electrons to chlorofluorocarbons (CFCs) and hydrochlorofluorocarbons (HCFCs) are strongly enhanced by the presence of H2O ice. The absolute cross sections for CFCl3, CHF2Cl, and CH3CF2Cl on water ice are measured to be approximately 8.9 x 10(-14), approximately 5.1 x 10(-15), and approximately 4.9 x 10(-15) cm2 at approximately 0 eV, respectively. The former value is about 1 order of magnitude higher than that in the gas phase, while the latter two are 3-4 orders higher. In contrast, the resonances at electron energies > or = 2.0 eV are strongly suppressed either for CFCs and HCFCs or for CF4 adsorbed on H2O ice. The cross-section enhancement is interpreted to be due to electron transfer from precursor states of the solvated electron in ice to an unfilled molecular orbital of CFCs or HCFCs followed by its dissociation. This study indicates that electron-induced dissociation is a significant process leading to CFC and HCFC fragmentation on ice surfaces.

Large enhancement in dissociative electron attachment to HCl adsorbed on H2O ice via transfer of presolvated electrons

We report that dissociative electron attachment (DEA) to HCl is strongly enhanced by adsorption on the surface of H2O ice. The absolute DEA cross section at ∼0 eV for HCl adsorbed on ice is measured to be ∼4.0×10−15 cm2, which is two orders of magnitude higher than in the gas phase. This enhancement is essentially due to electron transfer from precursor states of the solvated electron in ice to an unfilled molecular orbital of HCl followed by its dissociation. This study indicates that electron-induced dissociation may be a significant process leading to HCl dissociation on ice surfaces in polar stratospheric clouds due to ionization by cosmic rays.

Effects and applications of ultrashort-lived prehydrated electrons in radiation biology and radiotherapy of cancer.

The subpicosecond-lived prehydrated electron (e(pre)(-)) is a fascinating species in radiation biology and radiotherapy of cancer. Using femtosecond time-resolved laser spectroscopy, we have recently resolved that e(pre)(-) states are electronically excited states and have lifetimes of approximately 180 fs and approximately 550 fs, after the identification and removal of a coherence spike, respectively. Notably, the weakly bound e(pre)(-) (< 0 eV) has the highest yield among all the radicals generated in the cell during ionizing radiation. Recently, it has been demonstrated that dissociative electron transfer (DET) reactions of e(pre)(-) can lead to important biological effects. By direct observation of the transition states of the DET reactions, we have showed that DET reactions of e(pre)(-) play key roles in bond breakage of nucleotides and in activations of halopyrimidines as potential hypoxic radiosensitizers and of the chemotherapeutic drug cisplatin in combination with radiotherapy. This review discusses all of these findings, which may lead to improved strategies in radiotherapy of cancer, radioprotection of humans and in discovery of new anticancer drugs.

Resonant dissociative electron transfer of the presolvated electron to CCl4 in liquid: Direct observation and lifetime of the CCl4*− transition state

We report a pump-probe femtosecond transient absorption spectroscopic study on the electron transfer reaction of CCl(4) in liquid ethanol. By direct observations of the presolvated electron and of the reaction transition state CCl(4) (*-), this study provides direct evidence of the resonant dissociative electron transfer (RDET) of the presolvated electron to CCl(4). Moreover, the lifetime of CCl(4) (*-) in ethanol is directly obtained from the decay kinetics and its measured value is found to be nearly identical to its gas-phase value. Hence, these results also imply that RDET can be an efficient process in an aqueous environment.

Direct observation of the transition state of ultrafast electron transfer reaction of a radiosensitizing drug bromodeoxyuridine

Replacement of thymidine in DNA by bromodeoxyuridine (BrdU) has long been known to enhance DNA damage and cell death induced by ionizing/UV radiation, but the mechanism of action of BrdU at the molecular level is poor understood. Using time-resolved femtosecond laser spectroscopy, we obtain the real-time observation of the transition state of the ultrafast electron transfer (ET) reaction of BrdU with the precursor to the hydrated electron, which is a general product in ionizing/UV radiation. The results show that the ET reaction is completed within 0.2 picosecond (ps) after the electronic excitation, leading to the formation of a transition state BrdU*- with a lifetime of approximately 1.5 ps that then dissociates into Br- and a high reactive radical dU*. The present results can greatly enhance our understanding not only of the mechanism of BrdU as a radio-/photosensitizer but of the role of prehydrated electrons in electron-initiated processes in biological and environmental systems.