[Formation of 8-hydroxyguanine upon damage of guanine nucleotides by gamma radiation]. / Obrazovanie 8-oksiguanina pri povrezhdenii guanilovykh nukleotidov pod deistviem gamma-izlucheniia.

Formation of 8-hydroxyguanine derivatives caused by the exposure of aqueous solutions of guanine nucleosides and nucleotides (Guo, dGuo, GMP, dGMP, GDP, and GTP) to gamma-radiation was studied by differential UV-spectroscopy. 8-hydroxyguanine had linear dose-yield relationship with G-value (radiation-chemical yield) of 0.2-0.4 molecules per 100 eV. Data on irradiation of D2O solutions of nucleotides show that the mechanism of gamma-radiation-induced formation of 8-hydroxyguanine is probably different from that of heat-induced one. Levels of intracellular guanine nucleotide pool damage caused by natural background radiation and induced by heat were compared for different temperatures. Level of DNA precursor pool damage by natural background radiation at 37 degrees C is insignificant and comprises approximately 0.2% of the heat-induced damage but rises sharply as the temperature decreases. The possible biological consequences of gamma-radiation-induced damage of guanine and deoxyguanine nucleotide cell pools are discussed.

The dose rate effects on the in vitro radiolysis products of magnesium-guanosine-5'-monophosphate complexes in aqueous solutions.

This study examined the effects on the radiolysis of magnesium-guanosine-5'-monophosphate complexes in deaerated aqueous solutions, investigated by Fourier transform infrared (FT-IR) spectroscopy. It was found that when the system was irradiated with a dose rate of 500 rad/min (low dose rate), the OH radicals, H atoms and hydrated electrons (eaq-) produced from radiolysis of water reacted mainly by addition to the double bonds C4 = C5 and N7 = C8 of guanine. When the dose rate was 23,800 rad/min (high dose rate) the electrons reacted further with the complex by addition to the carbonyl group, C6 = O, of guanine.

Magnesium perchlorate and cis-platinum as radiosensitizers in in vitro radiolysis of nucleotides.

The mechanism of the gamma-radiolysis of the nucleotide guanosine-5'-monophosphate (5'-GMP) in the presence of Mg++ ions and cis-platinum was investigated. From high performance liquid chromatography and spectroscopy studies it was found that the OH radicals, produced in irradiated aqueous solutions, reacted with 5'-GMP by addition to the double bonds and that Mg++ as well as cis-Pt sensitized the nucleotide to radiation damage. Furthermore, an important finding was the fact that when the irradiation took place in aerated solutions, the Mg++ ions, contrary to cis-Pt, did not seem to have any effect on the decomposition yield G(-5'-GMP). This result together with the sensitization (100% increase) observed in deaerated solutions led to the conclusion that irradiation in the presence of Mg++ may result in a more effective gamma-radiation therapy for tumours.

ESR/ENDOR study of guanosine 5'-monophosphate (free acid) single crystals X-irradiated at 10 K.

Single crystals of the free base of guanosine 5'-monophosphate were X-irradiated at 10 and at 65 K and investigated between these temperatures and room temperature using K-band ESR and ENDOR spectroscopy. Three free radicals were detected in this temperature range. Two of these were identified as the O6-protonated anion radical and the C8 H-addition radical. Both of these species were present immediately after irradiation at 10 K. The anion radical was formed in two slightly different conformations, of which one decayed at about 150 K and the second at about 250 K. No successor radicals could be detected following the decay of the anion radical. The C8 H-adduct was stable at all temperatures used. The use of partially deuterated crystals confirmed the assignments made and showed that the main pathway for the formation of the C8 H-adduct consisted of addition of a proton from an easily exchangeable site. It is suggested that the C8 H-adduct is formed subsequent to a primary oxidation event localized either at the guanine base or at a nearby water of crystallization. Possible mechanisms for the formation of this product are discussed.

[Molecular nature of the mutations in gene ADE2 in Saccharomyces cerevisiae yeasts. III. Determination of the correlation of the GC AT pairs in genes ADE1 and ADE2]. / Izuchenie molekuliarnoi prirody mutatsii v gene ADE2 u drozhzhei Saccharomyces cerevisiae. Soobshchenie III. Opredelenie sootnosheniia par GTs i AT v genakh ADE1 i ADE2.

Lethal and mutagenic effects and the nature of mutations induced by decay of 32P incorporated into yeast cell DNA as 32P-deoxyguanosine monophosphate (32PdGMP) and 32P-thymidine monophosphate (32P-TMP), were studied. The lethal efficiency per 32P decay is independent of a labelled nucleotide incorporated into DNA. However, the mutagenic efficiency in ADE1, ADE2 genes per 32P decay is approximately 3 times greater for 32PdGMP than for 32P-TMP. This suggests that ADE1, ADE2 genes contain about 3 times more GC base pairs than AT pairs. Variations in a relative frequencies of GC leads to AT and AT leads to GC transitions were obtained depending upon a nucleotide labelled.

tRNA thiolated pyrimidines as targets for near-ultraviolet-induced synthesis of guanosine tetraphosphate in Escherichia coli.

Illumination with near-ultraviolet light triggers synthesis of ppGpp (guanosine 3'-diphosphate 5'-diphosphate) not only in growing Escherichia coli cells containing the putative chromophore 4-thiouridine in their tRNAs [Ramabhadran, T. V and Jagger, J. (1976) Proc. Natl Acad. Sci. USA, 73, 59--69], but also in nuv- cells which lack 4-thiouridine. The burst of ppGpp in nuv- cells is, however, induced exclusively by light of wavelengths shorter than 350 nm. Its maximum level is half that obtained in the parental strain. This ppGpp synthesis is also under the control of the relA gene, indicating that it is due to the accumulation of uncharged tRNAs. A candidate likely to trigger this effect is a 5-methylaminomethyl-2-thiouracil residues present in the first position of the anticodon loop of tRNAGlu, tRNALys and one tRNAGln isoacceptor. In conditions in vitro, this base is highly photoreactive at wavelengths shorter than 350 nm. Furthermore, near-ultraviolet-photomodified tRNAGlu and tRNALys become poor substrates of their acylation enzyme.

Application of polarography to the study of chemical radiosensitization of DNA components.

The half-wave reduction potentials of a range of nitroheterocyclic compounds were measured polarographically and compared with their radiosensitizing abilities in a simple radiation biochemical assay for damage to 5'-GMP. The chemical enhancement ratio for sensitization of inorganic phosphate release from irradiated 5'-GMP, increased with sensitizer electron affinity, but in a non-linear manner. An onset of sensitization was observed for nitroheterocyclics with half-wave potentials less negative then -0.05V vs. standard calomel electrode and maximum sensitization, approaching the oxygen effect, was obtained at a sensitizer half-wave potential of -0.25 V vs. standard calomel electrode. Nitroheterocyclic sensitizers with half-wave potentials in this range may be potential clinical radiotherapeutic agents.

Some parallelisms n the behavior of pancreatic ribonuclease and chicken lysozyme toward homopolyribonucleotides.

Pancreatic ribonuclease and chicken lysozyme possess gross similarities that are responsible for a common ability to form enormous light-scattering centers in cooperation with homopolyribonucleotides. The light-scattering power of the mixtures is highest when [homopolymer]/[protein] assumes some critical value that is unique for each homopolymer-protein pair. In some respects the scatterers resemble very large antigen-antibody networks. A criterion is established to ascertain the relative abilities of the homopolymers to form the centers with the two proteins. Both see polyinosinic acid (poly-I) as most and polyadenylic acid (poly-A) as least efficient in this respect.