Molecular mechanisms of radiation damage.DMITRI POPOV. PHD, RADIOBIOLOGY. MD (RUSSIA)ADVANCED MEDICAL TECHNOLOGY AND SYSTEMS INC. CANADA.

Molecular mechanisms of Acute Radiation Disease.

DOI: 10.13140/RG.2.1.4687.7924

Molecular mechanisms of acute and chronic radiation damage.

Lysosomes, lysosomal enzymes and are known to be involved in radiation induced damage of DNA and cancer develop processes. The lysosomes contain proteins and enzymes that would constitute pathways for the hydrolysis of proteins and peptides and DNA damage and mutations.

However, integrated biochemical and cell biology studies are necessary to understand how lysosomal enzymes combined with oxidant processes could initiate radiation damage and malignant consequences after irradiation.

Med Hypotheses. 2005;64(6):1170-2. Lysosomal and prostasomal hydrolytic enzymes and redox

processes and initiation of prostate cancer. Tappel A1.

Radiation Toxins.

Protease and phosphatase inhibitors are essential components of most cell lysis and protein extraction procedures.

These inhibitors block or inactivate endogenous proteolytic and phospholytic enzymes that are released from subcellular compartments during cells lysis and would otherwise degrade proteins of interest and their activation states.

https://www.thermofisher.com/ca/en/home/life-science/protein-biology/protein-biology-learning-center/protein-biology-resource-library/pierce-protein-methods/protease-phosphatase-inhibitors.html

Radiation Toxins. Molecular Mechanisms of Radiation.

Lysosomes are membrane-bound vesicles that contain digestive enzymes, such as glycosidases, proteases and sulfatases.

Lysosomal enzymes are synthesized in the endoplasmic reticulum (ER), are transported to the Golgi apparatus, and are tagged for lysosomes by the addition of mannose-6-phosphate label.

https://www.google.ca/webhp?sourceid=chrome-instant&ion=1&espv=2&ie=UTF-8#q=lysosomal%20enzymes

Radiation Toxins. Molecular Mechanisms of Radiation.

All living organisms contain proteolytic enzymes (proteases and peptidases).

In whole cells, protease and phosphatase activities are tightly regulated by compartmentalization or inhibitors to prevent indiscriminate damage to cellular proteins and to maintain proper function of signaling pathways.

Cell lysis disturbs the carefully controlled cellular environment, allowing proteases and phosphatases to become unregulated. The usual consequence of this unregulated state is reduced recovery of total protein.

https://www.thermofisher.com/ca/en/home/life-science/protein-biology/protein-biology-learning-center/protein-biology-resource-library/pierce-protein-methods/protease-phosphatase-inhibitors.html

Radiation Toxins. Molecular Mechanisms of radiation damage.

Lysosomes are cytoplasmic membrane-enclosed organelles containing hydrolytic enzymes that degrade macromolecules and cell components.

Lysosomes contain many different hydrolytic enzymes, including proteases, lipases, nucleases, glycosidases, phospholipases, phosphatases, and sulfatases, which usually exert maximal enzymatic activity at low pH.

Radiation Toxins. Molecular mechanisms of Acute Radiation Disease.

Several degradation pathways converge at the level of the lysosome, including endocytosis, phagocytosis, and autophagy.

Lysosomal Function and Dysfunction: Mechanism and Disease Patricia Boya. ANTIOXIDANTS & REDOX SIGNALING Volume 17, Number 5, 2012 ª Mary Ann Liebert, Inc. DOI: 10.1089/ars.2011.4405

Pathological degradation pathways initiated after moderate and high doses of radiation. http://www.intechopen.com/books/current-topics-in-ionizing-radiation-research/radiation-toxins-molecular-mechanisms-of-toxicity-and-radiomimetic-properties-

Radiation Toxins. Molecular Mechanisms of Acute Radiation Disease.

The mechanisms involved in radiation-induced cellular injury and death remain incompletely understood. In addition to the direct formation of highly reactive hydroxyl radicals (HO*) by radiolysis of water, oxidative stress events in the cytoplasm due to formation of H2O2 may also be important. Since the major pool of low-mass redox-active intracellular iron seems to reside within lysosomes, arising from the continuous intralysosomal autophagocytotic degradation of ferruginous materials, formation of H2O2 inside and outside these organelles may cause lysosomal labilization with release to the cytosol of lytic enzymes

Radiation-induced cell death: Importance of lysosomal destabilization. Hans Lennart Persson

University Hospital Linköping Division of Pulmonary Medicine, Faculty of Health Sciences, University of Linköping, S581 85 Linköping, Sweden.

Biochemical Journal (Impact Factor: 4.78). 09/2005; 389(Pt 3):877-84. DOI: 10.1042/BJ20050271Source: PubMed

Radiation Toxins and Molecular Mechanisms of Acute Radiation Disease.

It is increasingly recognised that IR-induced effects are not limited to the induction of nuclear DNA damage, but that a number of intracellular targets, such as lysosomes, can also be affected after exposure. The lysosome contains enzymes capable of catalysing the breakdown of intracellular material including DNA, lipids and protein

Evidence of a role for radiation-induced lysosomal damage in non-targeted effects: an experimental and theoretical analysis Scott Bright1 , Alexander G. Fletcher2 , David Fell1 , Munira A. Kadhim1,* 1 Department of Biological and Medical Sciences, Oxford Brookes University, Oxford, OX3 0BP, UK 2 Mathematical Institute, University of Oxford, Andrew Wiles Building, Radcliffe Observatory Quarter, Woodstock Road, Oxford OX2 6GG, UK

Radiation Toxins and Molecular Mechanisms of Acute Radiation Disease.

The invertase inhibitory protein isolated from Cyphomandra betacea Sendt and Solanum tuberosum inhibited the invertase activity from different species, genera and even plant family. Furthermore, proteinaceous inhibitors are not invertase specific; fungal, bacterial and higher plant enzymes including polygalacturonase, pectinase, pectin lyase, alpha-L-arabinofuranosidase and beta-glucosidase are also shown to be inhibited.

J Enzyme Inhib Med Chem. 2002 Feb;17(1):37-43. Inhibition of hydrolytic enzyme activities and plant pathogen growth by

invertase inhibitors. Isla MI1, Ordóñez RM, Moreno MI, Sampietro AR, Vattuone MA.

Radiation Toxins and Molecular Mechanisms of Acute Radiation Disease.

Antipain is clearly the most effective of the protease inhibitors studied here at suppressing radiation transformation. Antipain appears to inhibit all 3 phases of the transformation process, presumably reflecting an ability to inhibit more than one pro tease involved in this transformation system. It

[CANCER RESEARCH 41, 2103-2108, June 1981] 0008-5472/81 /0041-OOOOS02.00 Effects of Protease Inhibitors on Radiation Transformation in Vitro1 Ann R. Kennedy2 and John B. Little Laboratory of Radiobiology, Harvard University School of Public Health. Boston,

Massachusetts 02115

Radiation Toxins and Molecular Mechanisms of Acute Radiation Disease.

Troll, W., Meyn, M. S., and Rossman, T. G. Mechanisms of protease action in carcinogenesis. In: T. J. Slaga, A. Sivak, and R. K. Boutwell (eds.),

Carcinogenesis, Vol. 2, pp. 301-312. New York: Raven Press. 1978.

Troll, W., Rossman, T., Katz. J.. Levitz. M., and Sugimura. T. Proteinases in

tumor promotion and hormone action. Cold Spring Harbor Conf. Cell Proliferation, 2. 977-987, 1975.

Radiation Toxins and Molecular Mechanisms of Acute Radiation Disease.

Kennedy, A. R., and Little, J. B. Protease inhibitors suppress radiation induced malignant transformation in vitro. Nature (Lond.) 276. 825-826, 1978.

Radiation Toxins and Molecular Mechanisms of Acute Radiation Disease.

Antiradiation Vaccine: Immunological neutralization of Radiation Toxins at Acute Radiation Syndromes.

http://adsabs.harvard.edu/abs/2010cosp...38.3183P Current medical management of the Acute Radiation Syndromes

(ARS) does not include immune prophylaxis based on the Antiradiation Vaccine. Existing principles for the treatment of acute radiation syndromes are based on the replacement and supportive therapy. Haemotopoietic cell transplantation is recomended as an important method of treatment of a Haemopoietic form of the ARS. Though in the different hospitals and institutions, 31 pa-tients with a haemopoietic form have previously undergone transplantation with stem cells, in all cases(100%) the transplantants were rejected. Lethality rate was 87%.(N.Daniak et al. 2005). 

Radiation Toxins and Molecular Mechanisms of Acute Radiation Disease.

A large amount of biological substances or antigens isolated from bacterias (flagellin and derivates), plants, different types of venom (honeybees, scorpions, snakes) have been studied.

This biological active substances can produce a nonspecific stimulation of immune system of mammals and protect against of mild doses of irradiation.

But their ( exclude rattle snake venom) radioprotection efficacy against high doses of radiation were not sufficient.

http://adsabs.harvard.edu/abs/2010cosp...38.3183P

Radiation Toxins.

The Blocking Antiradiation Antibodies induce an immunologically specific effect and inhibiting effects on radiation induced neuro-toxicity, vascular-toxicity, gastrointestinal toxcity, hematopoietic toxicity. Antiradiation Antibodies prevent the radiation induced cytolysis of selected groups of cells that are sensitive to radiation. The Blocking Antiradiation Antibodies are immunologically specific and can be produced by immunization with the different radiation toxins isolated from irradiated mam-mals. We propose that Specific Antiradiation Antibodies targeted against the radiation induced Toxins. Specific Antiradiation Antibodies neutralize toxic properties of radiation toxins. Anti-radiation Antibodies in different phases of the Acute Radiation Syndromes can compete with cytotoxic lymphocytes and prevent cytolysis mediated by cytotoxic lymphocytes. Conclusions: Immunological inhibition of cytotoxic and neurotoxic properties of Specific Radiation Toxins are significant factors for improving results of Medical Management of severe forms of the ARS and will optimize results of traditional methods of therapy of the ARS. Immunological inhi-bition of Radiation Toxins must be a part of technical procedure before haemotopoietic stem cells transplantation. Positive therapeutic results of neutralization of SRD RT could make a procedure of haemopoietic stem cell transplantation efffective.

Radiation Toxins and Molecular Mechanisms of Acute Radiation Disease.

Journal of Radiation Research, 2013, 54, 243–250 doi: 10.1093/jrr/rrs098 Advance Access Publication 26 October 2012 Anti-radiation damage effect of polyethylenimine as a toll-like

receptor 5 targeted agonist. Polyethylenimine is a new human TLR5 agonist with potential

application in radiation protection, including, but not limited to, offering protection for cancer patients who receive radiotherapy or radiosurgery, and could serve as a new compound for protecting the health and safety of people in radiation-related accidents.

Zhiqiang HU1,2, † , Yaling XING1, † , Yuanyu QIAN3, † , Xiaojuan CHEN1, Jian TU4, Lening REN1,2, Kai WANG1 and Zhongbin CHEN1,*

Radiation Toxins and Molecular Mechanisms of Acute Radiation Disease.

http://www.slideshare.net/dlpopov/medical-management-of-acute-radiation-syndromes-comparison-of-antiradiation-vaccine-and-antioxidants-radioprotection-potency

http://www.slideshare.net/dlpopov/radiation-vs-rattle-snakebite http://www.slideshare.net/dlpopov/rad-toxhydrolyticenzymes http://

www.slideshare.net/dlpopov/radiation-toxicity-tolllike-receptors

Radiation Toxins and Molecular Mechanisms of Acute Radiation Disease.

Conclusion: Specific antibodies – possible antagonists of Toll like receptors and can inhibit massive activation of lysosomal hydrolytic enzymes and prevent radiation toxicity after high doses of Radiation.