CELL PROCESSES INDUCED BY IONISING RADIATION

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The inception of the radiobiological effect is

The act of interaction of ionizing radiation with matter

The products of the radiobiological effect are

Ionized and excited atoms and molecules, which experience further changes

The radiation damages are

Partial changes of organic macromolecules induced by ionizing radiation

Radiation damage may be due to

Direct action of radiation and indirect action

Direct action of ionizing radiation is

Radiation damage of biologically significant molecules resulting from a direct hit by an ionizing photon or particle

Indirect action of ionizing radiation is

Radiation damage of molecules resulting from their interactions with the products of radiation-induced reactions

Radiation-induced processes are

Primary: related to the direct action of ionizing radiation and Secondary: related to the indirect action of ionizing radiation

The primary processes are related mainly to the

Effect of ionizing radiation on water molecules and the primary products react with organic molecules – lipids, nucleic acids, proteins

Water radiolysis is

Decomposition of water molecules to relatively stable forms

Linear energy transfer is

The amount of energy transferred from the ionizing particle to material per unit distance traveled in the medium

At low linear energy transfer

Radicals are produced far from each other—they have strong effect on the molecules of the medium

At high linear energy transfer:

Radicals interact with each other—their effect on other molecules is smaller

Effects on nucleic acids induced by radiation:

Damage of single nucleotides, single-and double-strand breaks and covalent bonds

. Nucleotide damage is

Radiolysis of purine bases and breaks of pyrimidine rings, breaking of amino groups from cytosine, adenine and guanine, oxidation of deoxyribose alcohol groups

Strand Breaks are

Breaks of the polynucleotide strands producing OH-and PO4-ends; Breaks of hydrogen bonds in double-strand DNA and partial denaturation

Strand bonding create

Covalent bonds between bases and covalent bonds between the strands of the double helix

The effect of the ionizing radiation on cells depend on:

Dose absorbed and dose rate, cell type, environment parameters during exposure

Damages caused by ionizing radiation in cells are

Genetic changes of inheritable properties and in offspring and somatic changes of the exposed cell

Genetic effects because of the ionizing radiation

Gene(point) mutations - damage to single nucleotides; Chromosome mutations - damage to chromosomes; Genome mutations - changed number of chromosomes

Somatic effects because of the ionizing radiation

The most investigated somatic effect is the death of the cell and we have: Interphase death - the exposed cell dies and Proliferative death - the exposed cell cannot reproduce itself correctly; death after the first or a small number of cell divisions

Oxygen effect after influence of ionizing radiation

. Aggravation of radiation damage by oxygen, because of the interaction of oxygen with free radicals, producing aggressive peroxide radicals. Observed for macromolecules and other complex systems

The after-action of oxygen aggravation of radiation damage by oxygen introduced after the exposure mean

Radiation produces 'potential' damages, which are expressed by interaction with oxygen. The 'potential' damages are stable free radicals

Oxygen enhancement ratio is

The ratio of the effects caused by a given exposure (dose) with and without oxygen or the ratio of the doses producing the same effect without and with oxygen

The oxygen enhancement ratio depends on the

Absorbed dose; oxygen concentration; physiological state of cell; linear energy transfer L

. Modifiers of radiation damage:

Change the amount of primary products, deactivate/activate free radicals, stimulate/suppress repairs;

Types of modifiers by the change of the effect

Radiosensitizers—aggravate the effect and Radioprotectors—weaken the effect

Types of radioprotectors by the time of introduction

Preventive protectors—effective if introduced before exposure and Therapeutic protectors—effective if introduced after the exposure

Dose ratio is the

Ratio of the doses producing the same effect without and with modifier. For radioprotectors is K < 1, for radiosensitizers: K > 1;

Radiomimetics substances are substances

Effecting living cells in a way, similar to ionizing radiation. They have mutagenic and carcinogenic effect on cells

Effects of ionizing radiation on pure proteins:

Modifications of the amino acids in the protein macromolecule: splitting of a carboxyl group – breakage of C–C bond; Splitting of an amino group – breakage of C–N bond; If the protein contains Sulphur S–the damage is located at the Sulphur atom;

. Effects of ionizing radiation on proteins in water solutions

Secondary processes with the participation of OH and (e–)s. The excited states migrate along the entire polypeptide chain. Proteins decompose into amides and carbonyl compounds

Consequences of the ionizing radiation on the proteins

Denaturation of proteins, decreased protein activity, loss of binding specificity

Effects of ionizing radiation on lipids

Pure lipids decarboxylate on exposure and produce hydrocarbon radicals. Lipids in water solution produce radicals with unmatched electrons in the carboxyl and hydrocarbon parts of the molecule

Final products of the transformations of lipids because of the ionizing radiation

Carboxyl compounds, Aldehydes, Ketones, Alcohols, Carbon dioxide, Lipid peroxides

Radiation-induced chemical reactions in complex systems

Primary processes take place when the ionizing particle crosses the cell, secondary processes depend on the distribution of primary products, diffusion rate of the free radicals

Radiation chemical yield is

The number of molecules transformed by radiation-induced chemical reactions per 100 eV radiation energy absorbed. That is a quantitative characteristic of radiation-induced chemical processes