RU1808015C - Method of mammalian protection against gamma-irradiation - Google Patents

Abstract

Usage: radiobiologists, genetics, biologists, protection of the genome and erythropoiesis of animals from the mutagenic effect of radiation. The essence of the invention: the introduction of mice 30 minutes to 2 hours before gamma radiation (GI) at a dose of 1.5 Gy of copolymers in the most tolerated doses of MTD allows to reduce the mutagenic effects of GI by 53-55%, stimulate erythropoiesis in irradiated animals and completely eliminate inhibition of GI differentiation of erythroid cells. When exposed to external exposure to gamma radiation at a dose of 6 Gy, the introduction of copolymers in MTD allows increasing animal survival up to 100% (PE-12) and up to 50% (PE-13). An increase in AA units in the copolymer molecule allowed the toxicity of polyelectrolytes to be reduced by an order of magnitude.

Description

The invention relates to radiobiology and genetics and can be used in biology to protect the genome and erythropoies of animals from mutagenic effects of gamma radiation.

The aim of the invention is to protect the genome, erythropoiesis and vitality of mammals when exposed to gamma radiation.

The goal - inhibition of the mutagenic effects of gamma radiation - is achieved by the fact that 30 minutes - 2 hours before irradiation (1.5 Gy) mice are injected once peritoneally with aqueous solutions of PE-12 and PE-13 copolymers. The copolymers used are in the class of polyelectrolyte.

To increase the viability of animals 30 minutes before gamma radiation (6 Gy), mice were injected with aqueous solutions of PE-12 copolymers once intraperitoneally

and PE-13 at maximum tolerated doses (MTD).

The copolymer M, M-dimethyl, M, M-diallylammonium chloride (DMDAAH) and acrylic acid (AK) developed at the Institute of Chemical Chemistry, USSR Academy of Sciences, is widely used in various fields of science and technology. For example, said copolymer is used as additives having flocculant and desalting properties, and also as an antistatic component for auxiliary layers of black-and-white and x-ray film materials. The copolymer is obtained from inexpensive and affordable raw materials - domestic industries.

The copolymers with different ratios of DMDAAX and AK units were investigated. The copolymer with a 50% AK content was named PE-12, and with a 67.9% AK-PE-13 content.

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Examples of a specific embodiment of a method for protecting a mammalian genome and erythropoiesis from exposure to gamma radiation.

 Example 1. Mutagenic effects in mammals are assessed by the number of induced micro nuclei in polychromatophilic erythrocytes — reticulocytes (young forms) of the bone marrow of mice.

The method detects gamma radiation induced chromosome damage in mouse bone marrow erythroblasts. The first generation CBA x C57B1 / 6 hybrid mice are used. Gamma radiation induces at a dose of 1.5 Gy the number of micro nuclei, 30-40 times higher than their level in unirradiated animals.

30 minutes to 2 hours before irradiation, the mice are injected once intraperitoneally with an aqueous solution of copolymers in doses of PE-12 - 10-75 mg / kg, PE-13 -50-300 mg / kg of animal weight. The maximum tolerated doses (MTD) for PE-12 are 50 mg / kg, and for PE-13.250 mg / kg.

The copolymers introduced by intact animal at the indicated doses did not induce micro nuclei in reticulocytes (Tables 1 and 2).

PE-12 in MTD reduced the number of micro-nuclei in polychromatophilic erythrocytes of irradiated animals by 53-55%, PE-13 in MTD by 53-55%. The PDMDAAH polymer (base object) at the maximum tolerated dose (25 mg / kg) reduced the number of microcores by only 42% (Table 3).

Example 2. The toxicity of preparations for bone marrow cells - the blood-forming organ, as well as the effects of gamma radiation on erythropoiesis were evaluated by the ratio of young forms - polychromatophilic erythrocytes (reticulocytes) to mature spectrocytes. The number of reticulocytes was calculated for 500 mature forms of red blood cells. In intact animals, as a rule, 70-90 reticulocytes (0.7-0.9) are recorded per 100 mature red blood cells. When exposed to gamma radiation (1.5 Gy), the number of reticulocytes decreases to 40-60 per 100 mature forms (0.4-0.6).

The introduction of PE-12 and PE-13 copolymers into intact animals stimulated spectropoiesis, as a result of which the number of reticulocytes when using the MTD of PE-12 copolymer increased to 1.0-1.3, and PE-13 to 1.1-1, 7.

Administration of copolymers to mice 30 minutes to 2 hours prior to irradiation increased the number of reticulocytes: PE-12 - by 10%, PE13 - by 20%; the number of reticulocytes in irradiated animals exceeded their level in unirradiated animals.

. Example 3. The toxic effect of samples of copolymers on the body of animals (with a single intraperitoneal administration to mice) is characterized by the level of MTD.

The copolymers were administered to animals in a wide range of doses. MTDs not affecting animal viability were determined. With a decrease in toxicity, the antimutagenic effects of the copolymers increased in comparison with PDMDAAH and their stimulating effect on erythropoiesis increased.

Thus, a study of the toxic effect of copolymers with different ratios of DMDAAX and AK units showed that a shift in the direction of increasing the content of AA units in the copolymer leads to a significant decrease in the toxicity of the substance. The decrease in drug toxicity is probably associated with a decrease in the fraction of DMDAAX groups (32-50-%) in the copolymer molecule.

Example 4. The radioprotective effect of the copolymers on the animal organism was evaluated by the survival of FI mice (CBA x C57BI / 6) irradiated at a dose of 6 Gy (RUM-17 unit). The copolymers were administered to mice once intraperitoneally in MTD 30 minutes prior to irradiation. With total external irradiation of the body of animals in the specified dose, 10% of the mice survived (Table 5),

The preliminary (before irradiation) administration of the copolymers ensures the survival of 100% (PE-12) and 50% (PE-13) animals (observation period 45 days).

The use of a copolymer with an optimal ratio of DMDAAH and AK (PE-12) units completely protects the animal organism from a sublethal radiation dose. Moreover, the radioprotective effect is achieved by the use of a low toxic, stimulating erythropoiesis (unlike PDMDAAH polymer) compound.

Claims (1)

SUMMARY OF THE INVENTION A method for protecting mammals from exposure to gamma radiation, comprising intraperitoneal administration of an aqueous solution of the copolymer at the maximum permissible concentration for mice 30 minutes to 2 hours before irradiation, characterized in that the copolymers are copolymers M, M-dimethyl, M, M diallylammonium chloride and acrylic acid. Table The change in the number of micro nuclei in polychromatophilic erythrocytes (PCE) of the bone marrow of mice and the ratio of PCE: mature (A) after exposure to gamma radiation at a dose of 150 rad (1.5 Gy) and polyelectrolyte PE-12 P 0.05 The change in the number of micro-nuclei in polychromatophilic erythrocytes (PCE) of the bone marrow of mice and the ratio of PCE: mature red blood cells (A) after exposure to gamma radiation at a dose of 150 rad (1.5 Gy) and polyelectrolyte PE-13 P 0.05 Table 2 The effect of polyelectrolytes in maximum tolerated doses on the number of micro-nuclei induced by gamma radiation at a dose of 150 rad in polychromatophilic erythrocytes of mouse bone marrow  The ratio of PCE: mature red blood cells in intact animals is -0.88, the number of micro nuclei is 1.8 ± 0.68 Toxicity of polymelectrolytes Table3 Table E The effect of polyelectrolytes on the survival of live animals irradiated at a dose of 6 Gy (introduction copolymers 30 minutes before irradiation) Tableb