A fast Monte Carlo algorithm to simulate the spectrum of DNA damages formed by ionizing radiation

Ionizing radiation produces both singly and multiply damaged DNA sites. Multiply damaged sites (MDS) have been implicated in radiation-induced cell killing and mutagenesis. The spatial distribution of elementary damages (strand breaks and base damages) that constitute MDS is of special interest, since the complexity of MDS has an impact on damage repair. A fast and easy-to-implement algorithm to simulate the local clustering of elementary damages produced by ionizing radiation is proposed. This algorithm captures the major trends in the DNA damage spectrum predicted using detailed track- structure simulations. An attractive feature of the proposed algorithm is that only four adjustable parameters need to be identified to simulate the formation of DNA damage. A convenient recipe to determine the parameters used in the fast Monte Carlo damage simulation algorithm is provided for selected low- and high-LET radiations. The good agreement among the damage yields predicted by the fast and detailed damage formation algorithms suggests that the small-scale spatial distribution of damage sites is determined primarily by independent and purely stochastic events and processes.     

New monoclonal antibodies to 3 beta-hydroxy-gibberellins.

Two new monoclonal antibodies to 3 beta-hydroxy-gibberellins are described. Monoclonal antibodies GA1-1 and GA1-2 were derived from immunizations with the hapten-protein conjugate gibberellin A1-17-KLH. Cross-reactivities with a panel of 43 gibberellins and gibberellin derivatives are compared with those of other anti-gibberellin monoclonal antibodies.     

Serum bank as a component of system of biological safety

The concept of biological safety foresees prevention of potential and real biological hazard at different biorisk levels. In consideration are approaches for creation of a global monitoring, control and prognosis system of socially significant and dangerous infectious diseases with help of informative passported blood sera collection. The basic criteria of effective functioning of serum bank and computer base of the epidemiological data are the subject of discussion in a scope of update WHO requirements. Also new analytical systems for blood sera testing on the basis of protein microchip technology are discussed.     

Monte Carlo simulation of base and nucleotide excision repair of clustered DNA damage sites. I. Model properties and predicted trends

DNA is constantly damaged through endogenous processes and by exogenous agents, such as ionizing radiation. Base excision repair (BER) and nucleotide excision repair (NER) help maintain the stability of the genome by removing many different types of DNA damage. We present a Monte Carlo excision repair (MCER) model that simulates key steps in the short-patch and long-patch BER pathways and the NER pathway. The repair of both single and clustered damages, except double-strand breaks (DSBs), is simulated in the MCER model. Output from the model includes estimates of the probability that a cluster is repaired correctly, the fraction of the clusters converted into DSBs through the action of excision repair enzymes, the fraction of the clusters repaired with mutations, and the expected number of repair cycles needed to completely remove a clustered damage site. The quantitative implications of alternative hypotheses regarding the postulated repair mechanisms are investigated through a series of parameter sensitivity studies. These sensitivity studies are also used to help define the putative repair characteristics of clustered damage sites other than DSBs.     

Combined use of Monte Carlo DNA damage simulations and deterministic repair models to examine putative mechanisms of cell killing

A kinetic repair-misrepair-fixation (RMF) model is developed to better link double-strand break (DSB) induction to reproductive cell death. Formulas linking linear-quadratic (LQ) model radiosensitivity parameters to DSB induction and repair explicitly account for the contribution to cell killing of unrejoinable DSBs, misrepaired and fixed DSBs, and exchanges formed through intra- and intertrack DSB interactions. Information from Monte Carlo simulations is used to determine the initial yields and complexity of DSBs formed by low- and high-LET radiations. Our analysis of published survival data for human kidney cells suggests that intratrack DSB interactions are negligible for low-LET radiations but increase rapidly with increasing LET. The analysis suggests that no class of DSB is intrinsically unrejoinable or that DSB reparability is not strictly determined by the number of lesions forming the DSB. For radiations with LET >110 keV/mum, the model predicts that the relative cell killing efficiency, per unit absorbed dose, should continue to increase, whereas data from published experiments indicate a reduced cell killing efficiency. This observation suggests that the Monte Carlo simulation overestimates the DSB yield beyond 110 keV/microm or that other biological phenomena not included in the model, such as proximity effects, are important. For 200-250 kVp X rays ( approximately 1.9 keV/microm), only about 1% of the one-track killing is attributed to intratrack binary misrepair interactions. The analysis indicates that the remaining 99% of the lethal damage is due to other types of one-track damage, including possible unrepairable, misrepaired and fixed damage. Compared to the analysis of the X-ray results, 48% of the one-track lethal damage caused by 5.1 MeV alpha particles (approximately 88 keV/microm) is due to intratrack DSB interactions while the remainder is due to other forms of one-track damage.     

A monoclonal antibody against tyrosine hydroxylase: application in light and electron microscopy

The catecholaminergic neurons of the nervous system have been studied histochemically with fluorescent derivatives of catecholamines and immunocytochemically using antibodies against their biosynthetic enzymes. The immunocytochemical techniques yield permanent preparations and make possible ultrastructural studies and combined applications with other procedures. In this report, we describe the production and application of a high-affinity mouse monoclonal antibody against the rate-limiting enzyme in the biosynthetic pathway of the catecholamines, tyrosine hydroxylase. This antibody, coded TOHA1.1, has been used successfully to stain tyrosine hydroxylase immunoreactive sites in the known catecholaminergic neurons and fiber systems of rat brain in both light and electron microscopy. It has also been demonstrated that TOH A1.1 will immunoprecipitate phosphorylated tyrosine hydroxylase.     

Gene library of Dunaliella salina, prepared in a cosmid vector of new design]

The gene library (56,160 clones) of the halotolerant alga Dunaliella salina was obtained using a novel cosmid vector pBbv-cosII. The mean size of the insertions is 35-45 kb. Hybridization screening demonstrated that both nuclear and chloroplast DNA-containing clones are presented in the library.     

NO-inhibiting activity of radioprotectors

The effect of radioprotectors of different structure on the syntheses of nitric oxide induced by endotoxin in mice was studied. Using ESR-spectroscopy and spin trap techniques, it was shown that compounds of different chemical structure, such as aminothiols, isothiuronium derivatives, thiazolines, indolylalkylamines and others, suppressed the nitric oxide production in a whole body. The analysis of the relevant literature has confirmed the phenomenon described by the authors: radioprotectors show NO-inhibiting activity.     

Evaluation of amixine reactivity and efficacy for prophylaxis of acute respiratory tract infections]

Amixine reactivity and tolerability were evaluated in controlled trial at the risk group of medical personal at the period of flu and respiratory viral infection season. Drugs safety was estimated according to anamnesis, direct observation and hemogram. High efficacy of the drug for the infections prophylaxis and treatment was demonstrated. The drug was well tolerated and had no side effects. Amixine unreactivity was proved.