Green tea catechins partially protect DNA from (.)OH radical-induced strand breaks and base damage through fast chemical repair of DNA radicals.

The catechins, (-)-epicatechin (EC), (-)-epigallocatechin (EGC), (-)-epicatechin gallate (ECG) and (-)-epigallocatechin gallate (EGCG) are believed to be active constituents of green tea accounting for the reported chemoprevention of certain cancers. The molecular mechanisms by which the measured low concentrations (ca. micromolar) of catechins in humans can reduce the incidence of carcinogenesis is not clear. Using an in vitro plasmid DNA system and radiolytically generating reactive oxygen species (ROS) under constant scavenging conditions, we have shown that all four catechins, when present at low concentrations, ameliorate free radical damage sustained by DNA. A reduction in both prompt DNA single-strand breaks and residual damage to the DNA bases, detected by subsequent incubation with the DNA glycosylases formamidopyrimidine (FPG), endonuclease III (EndoIII) and 5' AP endonuclease exonuclease III (ExoIII), was observed. EGCG was found to be the most active of the catechins, with effects seen at micromolar concentrations. Combined fast-reaction chemistry studies support a mechanism of electron transfer (or H-atom transfer) from catechins to ROS-induced radical sites on the DNA. These results support an antioxidant role for catechins in their direct interaction with DNA radicals.

Reduction in free-radical-induced DNA strand breaks and base damage through fast chemical repair by flavonoids.

This paper provides evidence that dietary flavonoids can repair a range of oxidative radical damages on DNA, and thus give protection against radical-induced strand breaks and base alterations. We have irradiated dilute aqueous solutions of plasmid DNA in the absence and presence of flavonoids (F) in a "constant *OH radical scavenging environment", k of 1.5 x 10(7) s(-1) by decreasing the concentration of TRIS buffer in relation to the concentration of added flavonoids. We have shown that the flavonoids can reduce the incidence of single-strand breaks in double-stranded DNA as well as residual base damage (assayed as additional single-strand breaks upon post-irradiation incubation with endonucleases) with dose modification factors of up to 2.0+/-0.2 at [F] < 100 microM by a mechanism other than through direct scavenging of *OH radicals. Pulse radiolysis measurements support the mechanism of electron transfer or H* atom transfer from the flavonoids to free radical sites on DNA which result in the fast chemical repair of some of the oxidative damage on DNA resulting from *OH radical attack. These in vitro assays point to a possible additional role for antioxidants in reducing DNA damage.

Redox chemistry of the 9-anilinoacridine class of antitumor agents.

9-Anilinoacridines bearing a 1'-NHR substituent on the anilino ring undergo facile, chemically reversible, two-electron oxidation to quinone diimines. The chemical and electrochemical oxidation of three groups of 9-anilinoacridines (1'-substituted derivatives, together with 3'-substituted analogues and acridine-substituted analogues of the clinical antileukemic drug amsacrine) have been studied and their redox potentials determined. For aniline-substituted derivatives, redox potentials (E1/2) correlate well with substituent electronic properties, with electron-donating substituents facilitating oxidation. Substituents in the acridine ring have little effect on redox potentials, indicating minimal transmission of electronic effects from the acridine to the aniline rings. Although the broad class of 9-anilinoacridines show biological activity over a very wide range of structural variations, a 1'-NHR substituent is a common feature of the most active derivatives. Nevertheless, no clear quantitative relationships between redox potential and biological activity could be discerned, and the relevance of this redox chemistry to the mode of action of amsacrine and other 9-anilinoacridines remains unclear.

Reaction of the trichloromethyl and halothane-derived peroxy radicals with unsaturated fatty acids: a pulse radiolysis study.

The absolute rates of reaction of the trichloromethylperoxy radical, CCl3OO., derived from carbon tetrachloride and the halothane peroxy radical, CF3CHClOO., with oleic, linoleic, linolenic and arachidonic acids have been determined using the fast reaction technique of pulse radiolysis. In general, the rates of reaction of the radical derived from carbon tetrachloride are approximately five times greater than those for the halothane related radical. In both cases the rate constant increases with increasing unsaturation of the fatty acid in agreement with the known greater susceptibility of polyunsaturated fatty acids to peroxidative decomposition.

Reactions of the trichloromethylperoxy free radical (Cl3COO) with tryptophan, tryptophanyl-tyrosine and lysozyme.

The trichloromethyl peroxy radical Cl3COO reacts with tryptophan, tryptophanyl-tyrosine and with lysozyme to form products whose overall absorption spectrum is different from those observed following the reaction of hydroxyl, bromide, thiocyanate or azide radicals. Two spectral components have been identified: a minor component attributed to the neutral tryptophanyl radical which can react with ascorbate and intramolecularly with tyrosine residues and a major component which does not undergo either of these reactions and is probably a radical adduct.