Yimin Shi

Fast repair of DNA radicals

This tutorial review highlights the mechanism of a novel non-enzymatic fast repair of DNA damage, which refers exclusively to repair DNA radicals including DNA-OH* adducts, DNA radical cations and anions by various endogenous, natural and synthetic compounds. The repair rate constants are as high as 10(9) M(-1) s(-1). In cells, when the enzymatic repair system was inhibited or before the enzymatic repair mechanism was initiated, DNA oxidative damage was significantly reduced by natural polyphenols. This decrease of DNA damage is assigned to the fast repair. Fast repair takes place through an electron transfer process, and docking of polyphenol into the DNA minor groove could be the essential step.

Fast repair of deoxynucleotide radical cations by phenylpropanoid glycosides (PPGs) and their analogs.

The repair effects on deoxynucleotide radical cations of phenylpropanoid glycosides (PPGs) and their analogs, isolated from a Chinese folk medicinal herb, were studied using the pulse radiolysis technique. The radical cations of deoxynucleotides were formed by the reaction of SO4*- with deoxynucleotides. On pulse irradiation of a nitrogen saturated deoxynucleotide aqueous solution containing 20 mM K2S2O8, 200 mM t-BuOH and one of the PPGs or their analogs, the transient absorption spectra of the radical cations of nucleotide decayed with the formation of those of the radical cation of PPGs or their analogs within several tens of microseconds after electron pulse irradiation. The result indicates that deoxynucleotide radical cations can be repaired by PPGs or their analogs. The rate constants of the repair reactions were determined to be 0.48-1.1 x 10(9), 0.64-1.80 x 10(9) and 2.12-4.4 x 10(9) M(-1) s(-1) for dAMP, dGMP and dCMP radical cations respectively. It is obvious that the rate constants of the repair reaction depend on the number of phenolic hydroxyl groups contained in the PPGs and their analogs. A deeper understanding of this new repair mechanism will undoubtedly help researchers design strategies to prevent and/or intervene more effective in free radical related diseases.

Fast repair of deoxythymidine radical anions by two polyphenols: rutin and quercetin

The effects of rutin and quercetin on the repair of the deoxythemindine radical anion (dT*) were studied using the technique of pulse radiolysis. The radical anion of dT was formed by the reaction of hydrated electron with dT. After pulse irradiation of nitrogen-saturated aqueous solutions containing dT, 0.2M t-BuOH and either rutin or quercetin, the initially formed dT*(-), detected spectrophotometrically, rapidly decayed with the concurrent formation of the radical anion of rutin or quercetin. The results indicated that dT*(-) can be rapidly repaired by rutin or quercetin. The rate constants of the repair reactions were determined to be 3.1 and 4.1 x 10(9)M(-1)s(-1) for rutin and quercetin, respectively. With substitution by glycosyl groups at C(3)-OH bond being neighbor to C(4) keto group, which is the active site for electron transfer, rutin has a lower repair reaction rate constant toward dT*(-) than quercetin. Together with findings from our previous studies, the present results demonstrated that nonenzymatic fast repair may be a universal form of repair involving phenolic antioxidants.

In vivo non-enzymatic repair of DNA oxidative damage by polyphenols

The non‐enzymatic repair of DNA oxidative damage can occur in a purely chemical system, but data show that it might also occur in cells. Human hepatoma cells (SMMC‐7721) and human hepatocyte cells (LO2) were treated with 200 μM H2O2 for 30 min to induce oxidative DNA damage quantified by amount of 8‐OHdG and degree of DNA strand breaks, without inducing enzymatic repair. The dynamics of enzymatic repair activity quantified by unscheduled DNA synthesis, within 30 min after removal of H2O2 enzymatic repair mechanism has not been initiated. However, pre‐incubation with low micromolar level polyphenols, quercetin or rutin can significantly attenuate DNA damage in both cell lines, indicating that the polyphenols did not work through an enzymatic mechanism. Unscheduled DNA synthesis after removal of H2O2 was also markedly decreased by quercetin and rutin. Combined with our previous studies of fast reaction chemistry, the inhibitory effect of polyphenols have to be assigned to non‐enzymatic repair mechanism rather than to enzymatic repair mechanism or antioxidant mechanism.

Fast repair of dAMP hydroxyl radical adduct by verbascoside via electron transfer

DNA damaged by oxygen radicals has been implicated as a causative event in a number of degenerative diseases, including cancer and aging. So it is very impotant to look for ways in which either oxygen radicals are scavenged prior to DNA damage or damaged DNA is repaired to supplement the cells’ inadequate repair capacity. The repair activity and its mechanism of verbascoside, isolated fromPedicularis species, towards dAMP-OH · was studied with pulse radiolytic technique. On pulse irradiation of nitrous oxide saturated 2 mmol/L dAMP aqueous solution containing verbascoside, the transient absorption spectrum of the hydroxyl adduct of dAMP decayed with the formation of that of the phenoxyl radical of verbascoside well under 100 microseconds after electron pulse irradiation. The result indicated that dAMP hydroxyl adducts can be repaired by verbascoside. The rate constants of the repair reaction was deduced to be 5.9 × 108 dm3 · mol-1 · s-1. A deeper understanding of this new repair mechanism will undoubtedly help researchers explore new prevent and/or intervening medicine.

Fast repair of purine deoxynucleotide radical cations by rutin and quercetin

Repair effects of rutin and quercetin on purine deoxynucleotide radical cations were studied using pulse radiolysis technique. On electron pulse irradiation of N2 saturated deoxynucleotide aqueous solution containing 20 mmol/L K2S2O8, 200 mmol/Lt-BuOH and rutin or quercetin, the transient absorption spectra of the deoxynucleotide radical cations decayed quickly. At the same time, the spectra of flavonoid phenoxyl radicals formed within several dozen microseconds. The results indicated that deoxynucleotide radical cations can be repaired by flavonoids. The rate constants of the repair reactions were 3.8 ×108-4.4 ×108 mol−1 · L · s−1 and 1.3×108-1.8×108 mol−1 · L · s−1 for dAMP and dGMP radical cations, respectively.

Electron transfer from purine deoxynucleotides to deoxynucleotides deprotonated radical cations: in aqueous solution

Abstract In aqueous solution, the deprotonated radical cations of dCMP, TMP and Poly C created by SO 4 − can react with dAMP at a close to diffusion control rate constants which indicates a rapid electron transfer from dAMP to deprotonated radical cations of deoxynucleotides. Analogous reaction was found to occur between the deprotonated radical cation of dAMP, dCMP, TMP or Poly C and dGMP. The rate constants were determined to be 0.64–1.3×10 8 M −1 s −1 for electron transfer from dAMP toward deprotonated radical cations and 1.2–3.3×10 8 M −1 s −1 for the case of dGMP. Thus, the electron loss center caused by one electron oxidant or by ionizing radiation will end up at guanine in DNA.

Reaction of hydroxyl radical with phenylpropanoid glycoside and its derivatives by pulse radiolysis

The reaction of hydroxyl radical with 1 phenylpropanoid glycoside (PPG), cistanoside C, and its 3 derivatives: 1-0-β-D-2-(p-hydroxyphenyl)-ethanyl-glucose, 6-O-(E)-femloyl-glucose and 6-O-(E)-p-hydroxy-cinnarnoylglucose isolated from folk medicinal herbs was investigated by pulse radiolysis technique respectively. The reaction rate constants were determined by analysis of built-up trace of absorption at λmax of specific transient absorption spectra of PPG and its derivatives upon attacking · OH. All four compounds react with · OH at close to diffusion controlled rate (1. 03 × 109-19.139 × 109 L · mol−1 · s−1), suggesting that they are effective · OH scavengers. The results demonstrated that the numbers of phenolic hydroxyl groups of PPG and its derivatives are directly related to their scavenging activities. By comparing the reaction rates of · OH with 1-O-β-D-2-(p-hydroxyphenyl)-ethanyl-glucose, 6-O-(E)-feruloyl-glucose or 6-O-(E)-p-hydroxy-cinnomoyl-glucose, it is evident that the phenylethyl group is more impofiant than phenylacryloyl group for scavenging · OH.