Basic life sciences最新文献

Using a set of Monte Carlo simulation models, track structures of 125I Auger electrons generated in liquid water are superimposed on a nucleosome DNA model able to precisely localize energy deposition events on sub-molecular units of the DNA strands. After scoring direct hits taking place during the physical phase (at about 10(-15) s) the radiation chemistry of the whole system is simulated between 10(-12) and 10(-8) s, taking into account all reactions between water radio-chemical species, radicals, sub-molecular units of DNA (Ribose, Adenine, Thymine, Guanine, and Cytosine), and scavengers like Tris or Formate ions. The model's possibility to distinguish between direct and indirect hits has been utilized to introduce different assumptions for strand break induction by both hit modes. The number of SSB and DSB as well as their local distribution will be given and compared with experimental and theoretical results from the literature.

We have developed a computer monitor of nuclear DNA in the form of chromatin fibre. The fibres are modeled as a ideal solenoid consisting of twenty helical turns with six nucleosomes per turn. The chromatin model, in combination with are Monte Carlo theory of radiation damage induces by charged particles, based on general features of tack structure and stopping power theory, has been used to evaluate the influence of DNA structure on initial damage. An interesting has emerged from our calculations. Our calculated results predict the existence of strong spatial correlations in damage sites associated with the symmetries in the solenoidal model. We have calculated spectra of short fragments of double stranded DNA produced by multiple double strand breaks induced by both high and low LET radiation. The spectra exhibit peaks at multiples of approximately 85 base pairs (the nucleosome periodicity), and approximately 1000 base pairs (solenoid periodicity). Preliminary experiments to investigate the fragment distributions from irradiated DNA, made by B. Rydberg at Lawrence Berkeley Laboratory, confirm the existence of short DNA fragments and are in substantial agreement with the predictions of our theory.

A theoretical framework is presented which provides a quantitative analysis of radiation induced translocations between the ab1 oncogene on CH9q34 and a breakpoint cluster region, bcr, on CH 22q11. Such translocations are associated frequently with chronic myelogenous leukemia. The theory is based on the assumption that incorrect or unfaithful rejoining of initial double strand breaks produced concurrently within the 200 kbp intron region upstream of the second abl exon, and the 16.5 kbp region between bcr exon 2 and exon 6 interact with each other, resulting in a fusion gene. for an x-ray dose of 100 Gy, there is good agreement between the theoretical estimate and the one available experimental result. The theory has been extended to provide dose response curves for these types of translocations. These curves are quadratic at low doses and become linear at high doses.

We describe Monte Carlo codes that simulate, event by event, the interaction of energetic electrons with a double-stranded DNA molecule and with the condensed water surrounding it. Both direct and indirect effects are treated explicitly . The cross-sectional input necessary in the transport codes was obtained via quantum-mechanical calculations of the dielectric response function epsilon(q, omega), of polycytidine. For each inelastic event on DNA we score the energy deposited locally, the position of the event and the moiety that underwent that event. This information provides a detailed picture of the spatial disposition of molecular alterations for DNA exposed to ionizing radiation.

Detailed Monte Carlo calculations provide a powerful tool for understanding mechanisms of radiation damage to biological molecules irradiated in aqueous solution. This paper describes the computer codes, OREC and RADLYS, which have been developed for this purpose over a number of years. Some results are given for calculations of the irradiation of pure water. Comparisons are presented between computations for liquid water and water vapor. Detailed calculations of the chemical yields of several products from X-irradiated, oxygen-free glycylglycine solutions have been performed as a function of solute concentration. Excellent agreement is obtained between calculated and measured yields. The Monte Carlo analysis provides a complete mechanistic picture of pathways to observed radiolytic products. This approach, successful with glycylglycine, will be extended to study the irradiation of oligonucleotides in aqueous solution.

Cross section for kurbuc, a Monte Carlo track structure code simulating histories of electrons, interaction by interaction, in the energy range of 10 eV to 10 MeV, have been presented. Comparisons have been made for four independent Monte Carlo track structure codes for energetic electrons in gaseous and liquid water. The comparisons have been made in terms of point kernels for interactions and energy absorbed, and frequencies of energy depositions in cylindrical volumes of sizes similar to biological macromolecules. Comparisons have been made for 100 eV, 300 eV, 500 eV, 1 keV, 10 keV and 100 keV monoenergetic electrons. The four electron codes used in this study are moca8b and kurbuc for water vapour and orec and cpa100 for liquid water. A summary of cross sections, used in each code has been presented. The comparisons show similarities and differences in clustering properties of the four codes.

The male and female reproductive systems are targets for the toxicity of a wide range of compounds. There is a paucity of information regarding the modulating effects of antioxidants in such systems. Enzymically generated oxygen radicals have been shown to be toxic and/or mutagenic in a variety of in vitro test systems. It is known that vitamins C and E can modify responses in such systems. Malformations and growth reductions have been observed in whole rat embryo cultures in this laboratory after treatment with the oxygen radical generating system of xanthine/xanthine oxidase. Groups of 9.5-day-old rat embryos were treated with this system with or without vitamin C or E. Vitamin C at the doses given totally abolished neural suture defects while vitamin E only partially did so. Vitamins C and E administered alone had no effect on the embryos. Germ cell detachment has been shown to occur in mixed cultures of Sertoli and germ cells in response to some known in vivo testicular toxins. Such cultures were also treated with the oxygen radical generating system of xanthine/xanthine oxidase. There was an increase in germ cell detachment with this treatment which was reduced by vitamin C but not by vitamin E at the doses administered. These findings would suggest that vitamin supplementation could protect somatic cells of reproductive systems against toxins that act through oxygen radical mechanisms.