E. A. Krasavin

Meteorite-catalyzed syntheses of nucleosides and of other prebiotic compounds from formamide under proton irradiation

Significance Modern research on the origin of life started with Urey–Miller’s 1953 report on the spontaneous formation of amino acids upon application of electric discharge on a model of the pristine Earth atmosphere. Formamide provides a chemically sound starting material for the syntheses of prebiotic compounds; its role in prebiotics is becoming recognized. Kiloparsecs-wide clouds of formamide were observed in the interstellar space. The energy sources for the syntheses explored so far were largely thermal, and the catalysts used were mostly terrestrial. In the presence of meteorites and with high-energy protons, we observe the production of unprecedented panels of nucleobases, sugars, and, most notably, nucleosides. Carboxylic acids and amino acids complete the recipe. These findings extend prebiotic plausible scenarios well beyond our planet. Liquid formamide has been irradiated by high-energy proton beams in the presence of powdered meteorites, and the products of the catalyzed resulting syntheses were analyzed by mass spectrometry. Relative to the controls (no radiation, or no formamide, or no catalyst), an extremely rich, variegate, and prebiotically relevant panel of compounds was observed. The meteorites tested were representative of the four major classes: iron, stony iron, chondrites, and achondrites. The products obtained were amino acids, carboxylic acids, nucleobases, sugars, and, most notably, four nucleosides: cytidine, uridine, adenosine, and thymidine. In accordance with theoretical studies, the detection of HCN oligomers suggests the occurrence of mechanisms based on the generation of radical cyanide species (CN·) for the synthesis of nucleobases. Given that many of the compounds obtained are key components of extant organisms, these observations contribute to outline plausible exogenous high-energy–based prebiotic scenarios and their possible boundary conditions, as discussed.

A quantitative model of the major pathways for radiation-induced DNA double-strand break repair

We have developed a model approach to simulate the major pathways of DNA double-strand break (DSB) repair in mammalian and human cells. The proposed model shows a possible mechanistic explanation of the basic regularities of DSB processing through the non-homologous end-joining (NHEJ), homologous recombination (HR), single-strand annealing (SSA) and two alternative end-joining pathways. It reconstructs the time-courses of radiation-induced foci specific to particular repair processes including the major intermediate stages. The model is validated for ionizing radiations of a wide range of linear energy transfer (0.2-236 keV/µm) including a relatively broad spectrum of heavy ions. The appropriate set of reaction rate constants was suggested to satisfy the kinetics of DSB rejoining for the considered types of exposure. The simultaneous assessment of several repair pathways allows to describe their possible biological relations in response to irradiation. With the help of the proposed approach, we reproduce several experimental data sets on γ-H2AX foci remaining in different types of cells including those defective in NHEJ, HR, or SSA functions. The results produced confirm the hypothesis suggesting existence of at least two alternative Ku-independent end-joining pathways.

The effects of irradiation by 12C carbon ions on monoamine exchange in several rat brain structures

Rats were irradiated with carbon ions (12C) in a Nuklotron accelerator. The irradiation dose was 1 Gy, the energy of the ions was 500 MeV/nuclon, and the linear energy transmission (LET) was 10.6 keV/micron. The animals were decapitated 1 day after irradiation. We isolated the prefrontal cortex, nucleus accumbens, hypothalamus, hippocampus, and striatum, where we determined the concentrations of monoamines and their metabolites. Strong changes were observed in three structures, viz., the prefrontal cortex, nucleus accumbens, and hippocampus. However, significant changes were found in the prefrontal cortex and weaker changes were seen in the nucleus accumbens, whereas changes were insignificant in the hippocampus. This reaction may be related to the fact that the animals were examined on the 2nd day after irradiation. It was shown that an increase in the interval between irradiation and examination of animals results in enhancement of the effects of radiation treatment. The experiments revealed the high sensitivity and reactivity of the prefrontal cortex, which we relate to the key role of this structure in vitally critical processes of behavior.

The effect of high-energy protons in the Bragg Peak on the behavior of rats and the exchange of monoamines in some brain structures

We studied the effects of irradiation with protons at doses of 1 and 2 Gy in the Bragg Peak with an energy of 170 MeV on learning, recall of skills, and concentration of monoamines and their metabolites in the prefrontal cortex, nucleus accumbens, hypothalamus, striatum, and hippocampus of rats. In the T-maze, we performed discriminant learning with food reinforcement. Rats were trained for 5 days; from the second to fifth days, we found a considerable level of learning as compared to the first day. After training, on the sixth day, we found a trend to a decrease in the efficacy of test performance, which achieved significant differences on the seventh day of testing. Irradiation by protons at doses of 1 and 2 Gy in the Bragg peak did not influence the elaboration and recall of the passive avoidance reflex. This treatment causes a decrease in the concentration of catecholamines in the prefrontal cortex and 3-MT, a metabolite of dopamine, in the striatum. On the basis of disturbances of neurochemical indices in the corresponding brain structures, it is possible to logically explain the observed disturbances in behavior.

Proton irradiation: a key to the challenge of N-glycosidic bond formation in a prebiotic context

The formation of nucleosides in abiotic conditions is a major hurdle in origin-of-life studies. We have determined the pathway of a general reaction leading to the one-pot synthesis of ribo- and 2′-deoxy-ribonucleosides from sugars and purine nucleobases under proton irradiation in the presence of a chondrite meteorite. These conditions simulate the presumptive conditions in space or on an early Earth fluxed by slow protons from the solar wind, potentially mimicking a plausible prebiotic scenario. The reaction (i) requires neither pre-activated precursors nor intermediate purification/concentration steps, (ii) is based on a defined radical mechanism, and (iii) is characterized by stereoselectivity, regioselectivity and (poly)glycosylation. The yield is enhanced by formamide and meteorite relative to the control reaction.

The effects of high-energy protons and carbon ions ( 12 C) on the cognitive function and the content of monoamines and their metabolites in peripheral blood in monkeys

Model experiments using monkeys (rhesus macaque monkeys) were performed to investigate the neurobiological effects of two components of galactic cosmic radiation, namely, high-energy protons and carbon (12C) ions. It has been demonstrated that the irradiation of a monkey’s head with protons at a dose of 3 Gy did not cause any significant changes in the animal’s cognitive function and in the concentrations of monoamines and their metabolites in the peripheral blood. However, exposure to carbon ions at a dose of 1 Gy resulted in a significant cognitive function impairment and a significant decrease in serotonin metabolite concentrations in the blood in the monkeys with the excitable imbalanced type of higher nervous activity.

The dynamics of monoamine metabolism in rat brain structures in the late period after exposure to accelerated carbon ions

We studied the effect of carbon ions (12C) with an energy of 500 MeV/nucleon at a dose of 1 Gy on monoamine metabolism in the brains of rats of different ages. Neurochemical parameters that characterize the distribution of noradrenaline (NA), dopamine (DA), serotonin (5-HT), and its metabolites were evaluated during 2 months on days 30 and 90 after the exposure to radiation. We studied the prefrontal cortex, hypothalamus, hippocampus, and striatum. The results showed changes in the activities of the NA, DA, and 5-HT systems in rats of different age groups after exposure to radiation. The most prominent differences in the exposed and control animals were observed in the prefrontal cortex and hypothalamus, which indicates the important role of these brain regions in long-term effects of exposure to radiation on the central nervous system. A comparison of animals from different age groups showed a decrease in the intensity of the temporal changes in all analyzed structures except the striatum in the exposed rats. Based on these findings, we assumed that the activation of compensatory and repairing mechanisms occurs in the late post-radiation period. At relatively low linear energy transfer of particles (10.6 keV/µm), it may lead to the partial recovery of brain functions that were impaired by radiation. At higher values of the linear energy transfer, the compensatory and recovery processes are activated to a lesser degree and functional impairment increases with time.

The distribution of monoamines and their metabolites in the brain structures of rats at later periods after exposure to 12C ions

We investigated the levels of monoamines and their metabolites in certain brain structures of rats at 30 and 90 days after exposure to carbon ions (12C) with an energy of 500 MeV/nucleon. The linear energy transfer and radiation dose were 10.6 keV/µm and 1 Gy, respectively. The concentrations of substances were measured in five structures of the brain, including the prefrontal cortex, nucleus accumbens, hypothalamus, hippocampus, and striatum. On day 30 after the exposure, the most pronounced changes in the concentration of monoamines and their metabolites were observed in the nucleus accumbens; the smallest changes were found in the hippocampus and striatum. After 90 days, significant changes were still present in the nucleus accumbens. At the same time, these changes became less evident in other structures. A comparison of our results with the data of similar previous experiments (24 hours after exposure) showed that the most pronounced effect was observed soon after radiation exposure. The induced damage diminished at a later period. Based on the results of our study, we made the hypothesis that the change in the metabolism of monoamines may be compensated if the linear-energy transfer values were relatively low (10.6 keV/μm). At higher values of linear-energy transfer, compensatory and regenerative processes did not occur; the effect increased with time. An increased susceptibility of the nucleus accumbens was found at all the time points after the exposure, which may indicate an important role of this brain structure in the radiation-induced impairment of cognitive functions and emotional and motivational states.

Nonenzymatic Oligomerization of 3′,5′‐Cyclic CMP Induced by Proton and UV Irradiation Hints at a Nonfastidious Origin of RNA

We report that 3′,5′‐cyclic CMP undergoes nonenzymatic di‐ and trimerization at 20 °C under dry conditions upon proton or UV irradiation. The reaction involves stacking of the cyclic monomers and subsequent polymerization through serial transphosphorylations between the stacked monomers. Proton‐ and UV‐induced oligomerization of 3′,5′‐cyclic CMP demonstrates that pyrimidines—similar to purines—might also have taken part in the spontaneous generation of RNA under plausible prebiotic conditions as well as in an extraterrestrial context. The observed polymerization of naturally occurring 3′,5′‐cyclic nucleotides supports the possibility that the extant genetic nucleic acids might have originated by way of a straight Occamian path, starting from simple reactions between plausibly preactivated monomers.

Relationship between radioadaptive response and individual radiosensitivity to low doses of gamma radiation: an extended study of chromosome damage in blood lymphocytes of three donors

Abstract Purpose: Our study aimed at evaluating: 1) whether well-established variability in radioadaptive response (AR) in various donor blood lymphocytes might be attributed to inter-individual differences in radiosensitivity to different low dose levels; 2) whether AR is reproducibly present over time in the lymphocytes of AR-positive individuals. Experimental procedure: Whole blood samples of three donors were exposed to low doses (2–30 cGy) of γ-radiation alone (G0 phase) or followed by a 1 Gy challenge dose (late S/early G2 phase), and chromosome aberration were scored to assess the dose-response relationship and adaptive response, correspondingly. Three experiments were performed on blood samples of the same donors at six month intervals. Results: Significant differences in dose response relationship for blood lymphocytes were found among individuals. In most cases, the donors exhibited initial low-dose hypersensitivity (HRS) followed by an increase in radioresistance (IRR). AR could be successfully induced by some particular priming doses in the lymphocytes of each donor; however, the doses resulting in a protective response were quite different for all three donors. These protective doses could equally belong to either HRS or IRR region on the individual dose-response curves. In most cases, no clear AR outcome dependence on the priming dose was found at all. Moreover, pre-exposure to the same low dose could result in opposite effects in the lymphocytes of the same donor in different experiments. Conclusions: AR variability in human lymphocytes is not attributed to variation in radiosensitivity among individuals and is more drastic than was believed. It seems doubtful that AR is a universal phenomenon which has a consistent impact on the effects of radiation exposure on humans.