Role of secondary low-energy electrons in the concomitant chemoradiation therapy of cancer

Solid films of DNA with and without the chemotherapeutic agent cisplatin bonded to guanine were bombarded with electrons of 1, 10, 100, and 60,000 eV causing single and double strand breaks. In the presence of cisplatin this damage was increased by factors varying from 1.3 to 4.4 owing to an increase in bond dissociation triggered by the formation of transient anions. This mechanism may lie at the basis of the efficiency of concomitant cisplatin-radiation therapy.     

Induction of strand breaks by low-energy electrons (8-68 eV) in a self-assembled monolayer of oligonucleotides: effective cross sections and attenuation lengths

Self-assembled monolayers of 5'-32P-labeled 3'-thiolated oligonucleotides chemisorbed on gold were bombarded by low-energy electrons (LEE) of 8-68 eV. Shorter 5'-32P-oligonucleotides produced by LEE-induced strand breaks were separated with denaturing polyacrylamide gel electrophoresis and quantified by phosphor imaging. The yields of short oligonucleotides (y) decrease exponentially with their length (n), following the equation y=ae-bn, where a and b are constants, which are related to the average effective cross section per nucleotide for DNA strand break (sigmaeff) and the attenuation length (AL=1b) of LEE, respectively. The AL decreases with LEE energies from 2.5+/-0.6 nm at 8 eV to 0.8+/-0.1 nm at 68 eV, whereas sigmaeff increases from (3+/-1)x10(-18) to (5.1+/-1.6)x10(-17) cm2 within the same energy range. The energy dependence of sigmaeff shows a resonance peak of (2.8+/-0.9)x10(-17) cm2 at 18 eV superimposed on a monotonically rising curve. Transient electron attachment to a sigma* anion state of the deoxyribose group, followed by dipolar dissociation into H- and the corresponding positive-ion radical, leading to C-O bond cleavage, is proposed to account for this maximum.     

Glycosidic bond cleavage of thymidine by low-energy electrons

Thymidine was exposed to low-energy electrons (LEE) as a thin solid film under a high vacuum. Nonvolatile radiation products, remaining on the irradiated surface, were analyzed by HPLC/UV and GC/MS. Here, we show that exposure of thymidine to 3-100 eV electrons gives thymine as a major product with a yield of 3.2 x 10-2 per electron (about one-third of the total decomposition of thymidine). The formation of thymine indicates that LEE induces cleavage of the glycosidic bond separating the base and sugar moieties, suggesting a nonionizing resonant process involving dissociative attachment (<15 eV). In contrast, this reaction is not very efficient by DNA base ionization and does not occur by the reaction of solvated electrons with DNA. These studies introduce a new mechanism of DNA damage involving the interaction of LEE.     

Simplices by point-sliding and the Yamnitsky-Levin algorithm

Yamnitsky and Levin proposed a variant of Khachiyan's ellopsoid method for testing feasibility of systems of linear inequalities that also runs in polynomial time but uses simplices instead of ellipsoids. Starting with then-simplexS and the half-space {x¦a ^Tx }, the algorithm finds a simplexS _YL of small volume that enclosesS {x¦a ^Tx }. We interpretS _YL as a simplex obtainable by point-sliding and show that the smallest such simplex can be determined by minimizing a simple strictly convex function. We furthermore discuss some numerical results. The results suggest that the number of iterations used by our method may be considerably less than that of the standard ellipsoid method.     

Semilattices of proper inverse semigroups

Given a semilattice Y of inverse semigroups S, there corresponds a semilattice Y of groups G in a natural way. This correspondence is used to study semilattices of proper inverse semigroups. In paticular, it is shown that if S is a semilattice of proper inverse semigroups, then there exists a minimum semilattice congruence such that each -class is proper and there exists a maximum semilattice congruence such that each -class is proper.     

Dissociative electron attachment to DNA

Electron-stimulated desorption of anions from thin films of linear and supercoiled DNA is investigated in the range 3-20 eV. Resonant structures are observed with maxima at 9.4+/-0.3, 9.2+/-0.3, and 9.2+/-0.3 eV, respectively, in the yield dependence of H-, O-, and OH- on the incident electron energy. Their formation is attributed to dissociative electron attachment.     

The effect of bromine scanning around the phenyl group of 4‐phenylquinolone derivatives

Three quinolone compounds were synthesized and crystallized in an effort to study the structure–activity relationship of these calcium‐channel antagonists. In all three quinolones, viz. ethyl 4‐(4‐bromophenyl)‐2,7,7‐trimethyl‐5‐oxo‐1,4,5,6,7,8‐hexahydroquinoline‐3‐carboxylate, (I), ethyl 4‐(3‐bromophenyl)‐2,7,7‐trimethyl‐5‐oxo‐1,4,5,6,7,8‐hexahydroquinoline‐3‐carboxylate, (II), and ethyl 4‐(2‐bromophenyl)‐2,7,7‐trimethyl‐5‐oxo‐1,4,5,6,7,8‐hexahydroquinoline‐3‐carboxylate, (III), all C₂₁H₂₄BrNO₃, common structural features such as a flat boat conformation of the 1,4‐dihydropyridine (1,4‐DHP) ring, an envelope conformation of the fused cyclohexanone ring and a bromophenyl ring at the pseudo‐axial position and orthogonal to the 1,4‐DHP ring are retained. However, due to the different packing interactions in each compound, halogen bonds are observed in (I) and (III). Compound (III) crystallizes with two molecules in the asymmetric unit. All of the prepared derivatives satisfy the basic structural requirements to possess moderate activity as calcium‐channel antagonists.     

Phosphodiester and N-glycosidic bond cleavage in DNA induced by 4-15 eV electrons

Thin molecular films of the short single strand of DNA, GCAT, were bombarded under vacuum by electrons with energies between 4 and 15 eV. Ex vacuo analysis by high-pressure liquid chromatography of the samples exposed to the electron beam revealed the formation of a multitude of products. Among these, 12 fragments of GCAT were identified by comparison with reference compounds and their yields were measured as a function of electron energy. For all energies, scission of the backbone gave nonmodified fragments containing a terminal phosphate, with negligible amounts of fragments without the phosphate group. This indicates that phosphodiester bond cleavage by 4-15 eV electrons involves cleavage of the C-O bond rather than the P-O bond. The yield functions exhibit maxima at 6 and 10-12 eV, which are interpreted as due to the formation of transient anions leading to fragmentation. Below 15 eV, these resonances dominate bond dissociation processes. All four nonmodified bases are released from the tetramer, by cleavage of the N-glycosidic bond, which occurs principally via the formation of core-excited resonances located around 6 and 10 eV. The formation of the other nonmodified products leading to cleavage of the phosphodiester bond is suggested to occur principally via two different mechanisms: (1) the formation of a core-excited resonance on the phosphate unit followed by dissociation of the transient anion and (2) dissociation of the CO bond of the phosphate group formed by resonance electron transfer from the bases. In each case, phosphodiester bond cleavage leads chiefly to the formation of stable phosphate anions and sugar radicals with minimal amounts of alkoxyl anions and phosphoryl radicals.