Авторы

  • Ахрор Самадов
    Bukhara State Medical Institute named after Abu Ali ibn Sina

DOI:

https://doi.org/10.71337/inlibrary.uz.imjrd.100844

Аннотация

Depending on the radiation dose and its distribution throughout the human or animal body, the timing and causes of their death vary. The most common is the bone marrow form of acute radiation sickness, and depending on the type of mammal, death occurs 7-30 days after exposure, and the causes of death are most often hemorrhagic syndrome or infectious complications [3, 10, 11].


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UDK :615.849.5 - 036.11/.12 : 616.15-097 : 576.3 - 076.3

ANALYSIS OF THE RESULTS OF CYTOGENETIC EXAMINATION OF BONE

MARROW UNDER EXPERIMENTAL IRRADIATION

Samadov Axror Axmadovich

Email: samadov.axror@bsmi.uz https://orcid.org/0009-0007-2380-2531

Bukhara State Medical Institute named after Abu Ali ibn Sina, Uzbekistan, Bukhara, st. A.

Navoi. 1 Tel: +998 (65) 223-00-50 e-mail: info@bsmi.

Key words:

acute radiation, chronic radiation, cytogenetic analysis of bone marrow, white

outbred rats.
Depending on the radiation dose and its distribution throughout the human or animal div, the

timing and causes of their death vary. The most common is the bone marrow form of acute

radiation sickness, and depending on the type of mammal, death occurs 7-30 days after exposure,

and the causes of death are most often hemorrhagic syndrome or infectious complications [3, 10,

11].

Ionizing types of radiation include electromagnetic vibrations with a short wavelength, X-rays

and gamma radiation, streams of α- and β-particles (electrons), protons, positrons, neutrons and

other charged particles, α-radiation and X-ray radiation have a high penetrating power, β-radiation

has a lower penetrating power [5]. Radioactive substances can enter the div through intact skin,

gastrointestinal tract, and respiratory organs. After that, they are transported by blood and lymph

flow to organs and tissues [3, 9, 12].
It has been proven that the hematopoiesis system of the div is most susceptible to the effects of

radiation, especially for bone marrow cells. Under the influence of radiation, aplasia of the bone

marrow develops, inhibition of mitotic processes in the organs of hematopoiesis, and total death

of low-grade bone marrow cells. A decrease in hematopoiesis is accompanied by the appearance

of hemorrhagic syndrome [2, 5, 8].

Chronic radiation sickness is a complex clinical syndrome that develops in the case of prolonged

exposure to ionizing radiation in doses that exceed the permissible. Characteristic manifestations:

duration and undulation of the course; the presence in the clinical symptoms of both signs of

damage to the div from the effects of radiation, as well as manifestations of restorative and

adaptive reactions. Periods of development of chronic radiation sickness: the period of formation,

or actually chronic radiation sickness; the recovery period; the period of consequences of

radiation sickness [4, 7].

The aim of the study

was to study and evaluate cytogenetic changes in the bone marrow cells of

white outbred rats under chronic and acute experimental radiation in a comparative aspect.

Materials and methods of research.

To carry out the planned studies, 30 white mongrel rats

weighing 150-180 g of male were used, kept in standard vivarium conditions (room temperature

21-220 ° C, relative humidity 50-60%, light mode - 12 hours of darkness and light each). The

maintenance of laboratory animals, feeding and caring for them, selection of animals, cleaning

and disinfection of the vivarium premises were carried out according to Nuraliev N.A. et al. [6].
All laboratory animals (white mongrel rats) were obtained from the same nursery and of the same

age. Before the start of the experimental studies, all laboratory animals were kept in quarantine for


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21 days. When working with experimental animals, all ethical principles of working with

laboratory animals and rules of biological safety were strictly observed [1, 6].
All laboratory animals were divided into the following groups: The first group consisted of white

outbred rats (n=12) who received acute radiation once at a dose of 5 Gy; The second group

consisted of white outbred rats (n=12) who received chronic radiation for 20 days at 0.2 Gray

daily; The third group consisted of intact white outbred rats (n=6) who did not receive acute and

chronic radiation. During cytogenetic studies, all work with growth media and preparations was

carried out under sterile conditions using a laminar flow box. The buffers were prepared in

bidistilled water, filtered through membrane filters (0.22 microns "Millipor", Germany) and

autoclaved at 1.2 atm. 30 minutes. The glassware is pre-sterilized at 1600C for 120 minutes

before use. Equipment, fixtures, and tableware made of polymer materials were exposed to

ultraviolet light for 30 minutes. For experimental studies, bone marrow was selected from the

femur of white outbred rats during the autopsy of the animal.

Cytogenetic changes in rat bone marrow cells were studied using the direct method. The method

included the following steps: bone marrow was washed out of the femur of white outbred rats

involved in the experiment of all three study groups with RPMI 1640 nutrient medium with

0.04% colchicine (which destroys the spindle of division and chromosomes do not diverge to the

poles during mitosis, forming a polyploid organism) into a centrifuge tube and incubated for 2-2.5

hours in thermostat at 370C; incubated with hypotonic solution of CSl for 40 minutes in a

thermostat at 370C; after hypotonization, the fixative was treated three times in the proportion of

one part glacial acetic acid and three parts 96-1000 ethyl alcohol; the resulting precipitate was

applied to a pre-cleaned degreased slide and stained with Giems dye; metaphase search was

performed under a Leica microscope (Germany) at 200 magnification, metaphase plates were

analyzed at 1000 magnification, in each sample From 15 to 25 cells with metaphase plates were

analyzed. Statistical processing was carried out using generally accepted methods of variation

statistics using programs for statistical analysis of biomedical research. The significance level of

the indicator of the reliability of differences was considered to be P<0.05. When organizing and

conducting research, the principles of evidence-based medicine were observed.

Research results and their discussion

. For the analysis, we used bone marrow cells from

laboratory animals that received and did not receive different types of radiation, in which

elements of the mitotic apparatus were detected (Table).

Table
Results of cytogenetic analysis of bone marrow cells of white outbred rats exposed to acute and

chronic radiation

Group

Number of investigated

Polyploidy

Premature

condensation of

chromosomes

Dividing

cells

Metaphase

Prophase

First

group,

n=12

123

89 / 72,36

15 / 12,19

7 / 5,69

12 / 9,76

Second group,

n=12

125

60 / 48,0

11 / 8,80

3 / 2,40

51 / 40,80

Third

group, 75

75 / 100,0

0

0

0


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n=6

Note: the numerator is absolute; the denominator is relative (%)
In the first group (acute irradiation) of 123 bone marrow cells studied in laboratory animals,

72.36% (n=89) of the cells showed normal metaphase plates, 12.19% (n=15) of the cells were at

the prophase stage. It should be emphasized that 5.69% (n=7) of the cells had polyploid cells

(polyploidy), 9.76% (n=12) of the cells had premature condensation of chromosomes. Metaphase

plates are an accumulation of chromosomes in a plane perpendicular to the axis of division (the

equatorial plane), in which the chromosomes are equatorially located in the metaphase of mitosis

(the second phase of somatic cell division). The number of chromosomes in rats is normally 42

(diploid set).

Thus, the low content of cells (9.76%) with premature condensation of chromosomes and the

absence of cells with pulverization and scattering of chromosomes indicates minor changes in the

mitotic division of bone marrow cells in laboratory animals of this study group. The absence of

animals in this group with low cellular density and low blast transformation (8.3%, n=1) indicates

the normal mitotic activity of bone marrow cells in all (n=12) laboratory animals. There is no

pathology of mitosis in their bone marrow cells. Apparently, this fact is explained by the short

observation period (5 days) of animals after a single acute exposure, since, depending on the type

of mammal, death occurs on 7-30 days from the moment of exposure [2, 5].
The conducted studies have proved that after a single acute irradiation (5 Gray) during the first 5

days, there are practically no changes in the mitotic division of bone marrow cells, chromosomal

aberrations do not appear, and mitotic activity does not decrease.

Further, the same studies were conducted with white outbred rats that received chronic radiation

(the second group).

Of the 125 bone marrow cells studied in laboratory animals of the second group, normal

metaphase plates were found in 48.0% (n=60) of the cells, prophase stage was observed in 8.80%

(n=11) of the cells, polyploid cells were found in 2.40% (n=3) of the cases, and 40.80% (n=51) of

the cells Cells with premature condensation of chromosomes were observed.

Of the 12 animals of the second group, 1 rat (8.33%) did not have mitotically dividing cells on

the preparations, low cell count, low blast transformation and inhibition of mitosis were observed.

The presence of cells with pulverized chromosomes indicates a pathology of mitosis. The

presence of a high concentration of cells (40.80%) with premature condensation of chromosomes

in the bone marrow cells of rats of the second group indicates an inhibition of the normal mitotic

cycle, which affects the proliferative activity of this tissue and the presence of cell clones with

genetic pathology.

The following figures 1 (metaphase plate with normal karyotype) and 2 (normal early metaphase

plate) confirm the absence of changes in the microscopic picture of bone marrow cells in

laboratory animals that received a single acute radiation dose of 5 Gy on the 5th day after

irradiation.
Fig. 1. Bone marrow cells. A metaphase plate with a normal karyotype (the first group is acute

irradiation,

Approx.

x10,

Vol.


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x100).

In contrast to the laboratory animals of the first group, which were observed on the 5th day after

acute radiation, a different picture was observed in the second group of laboratory animals, which

were examined after 20 days of chronic radiation with a daily dose of 0.2 Gray. Pathology was

noted during bone marrow cell division.

Fig. 2. Bone marrow cells. Normal early metaphase plate (the first group is acute radiation,

Approx. x10, Vol. x100).
Figure 3 shows that the nucleus of an animal bone marrow cell belonging to the second group

contains an early phase with premature condensation of chromosomes. To the right and bottom of

the cell, which is visible in Fig. 3, there are interphase nuclei.


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Fig. 3. Bone marrow cell. Premature condensation of chromosomes (the second group was

chronic irradiation, Approx. x10, Vol. x100). In addition, a late phase of premature chromosome

condensation was also observed in the nucleus of bone marrow cells in laboratory animals (Fig. 4).

In another figure (Fig. 5), a nucleus with premature condensation is observed in the center of an

animal bone marrow cell after chronic irradiation. condensation of chromosomes, and interphase

nuclei are visible around it.
Fig. 4. Bone marrow cell. The nucleus has a late phase of premature chromosome condensation

(the

second

group

is

chronic

radiation,

Approx.

x10,

Vol.

x100).


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Fig. 5. Bone marrow cells. In the center is a nucleus with premature condensation of

chromosomes. There are interphase nuclei around (the second group is chronic radiation, Approx.

x10, Vol. x100).
The pathology of mitosis can also be observed in Fig. 6, where the nuclei with premature

condensation of chromosomes are visible in the center, and the nucleus with pulverization of

chromosomes is observed on the left (the second group is chronic radiation).

6. Bone marrow cells. In the center is a nucleus with premature condensation of chromosomes, on

the left is a nucleus with pulverized chromosomes (the second group is chronic radiation, Approx.

x10, Vol. x100).
Unlike laboratory animals of the first and second groups, which underwent acute and chronic

irradiation, no changes in bone marrow cells and the course of cell division were observed in the

bone marrow cells of white outbred rats of the third group (intact). In all cases, a normal

karyotype was found - late (Fig. 7) and early (Fig. 8) metaphase
.


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7. Bone marrow cells. Normal karyotype, late metaphase (the third group - without acute and

chronic radiation, Approx. x10, Vol. x100).
8. Bone marrow cells. Normal karyotype, early metaphase (the third group - without acute and

chronic radiation, Approx. x10, Vol. x100).

Thus, in laboratory animals after acute single exposure, the severity of cytogenetic changes was

less pronounced than in chronic exposure. There were no deviations from normal processes in

intact animals. Based on the conducted studies, cytogenetic changes in bone marrow cells of

laboratory animals exposed to acute and chronic radiation were studied and evaluated. The data

obtained make it possible to use the proposed recommendations to improve the effectiveness of

the methodology for studying and evaluating cytogenetic changes in bone marrow cells of

laboratory animals in experimental studies to determine the effect of different doses of radiation

on the div.

Conclusions.

1. In the first group (acute irradiation) of 123 bone marrow cells studied in laboratory animals,

normal metaphase plates were detected in 72.36% of the cells, 12.19% of the cells were at the


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prophase stage. It should be emphasized that 5.69% of cells were polyploid (polyploidy), 9.76%

of cells had premature condensation of chromosomes.

2. The low content of cells (9.76%) with premature condensation of chromosomes and the

absence of cells with pulverization and scattering of chromosomes indicates minor changes in the

mitotic division of bone marrow cells in laboratory animals of the first study group. The absence

of animals with low cellular density and low blast transformation (8.3%) indicates the normal

mitotic activity of bone marrow cells in all laboratory animals. Apparently, this is due to the short

observation period (5 days) of animals after acute irradiation, since it is assumed that, depending

on the type of mammal, death occurs on 7-30 days from the moment of irradiation.

3. Studies have proven that after a single acute irradiation (at a dose of 5 Gy) during the first 5

days, there is practically no pathology of mitosis (changes in the mitotic division of bone marrow

cells), chromosomal aberrations do not appear, and mitotic activity does not decrease. In this

regard, we believe that at this time it is possible to carry out therapeutic and preventive measures

to maintain the proliferation and differentiation of bone marrow cells, increase the activity of the

immune system.
4. Of the 125 bone marrow cells studied in white outbred rats of the second group (chronic

irradiation), normal metaphase plates were found in 48.0% of the cells, the prophase stage was

observed in 8.80% of the cells, polyploid cells were found in 2.40% of the cases, and cells with

premature chromosome condensation were observed in 40.80% of the cells. Of the 12 animals of

the second group, 1 rat (8.33%) did not have mitotically dividing cells on the preparations, low

cell count, low blast transformation and inhibition of mitosis were observed. The presence of cells

with pulverized chromosomes indicates a pathology of mitosis.

5. The presence of a high concentration of cells (40.80%) with premature condensation of

chromosomes in the bone marrow cells of rats of the second group indicates an inhibition of the

normal mitotic cycle, which affects the proliferative activity of this tissue and the presence of cell

clones with genetic pathology. 6. In laboratory animals, after acute single exposure, the severity

of cytogenetic changes was less pronounced than in chronic exposure. There were no deviations

from normal processes in intact animals.

List of used literature

1. Zharmukhamedova T.Yu., Semushina S.G., Pakhomova I.A., Pimenov M.S., Murashov A.N.

International rules of work with laboratory animals during preclinical tests // Toxicological

Bulletin. - Moscow, 2011. - №4(109). - P.2-9.
2. Ivanov A.A., Andrianova I.E., Maltsev V.N., Shalnova G.A., Stavrakova N.M., Bulynina T.M.,

Karaulova T.A., Bushmanov A.Yu., Ushakov I.B. Immuno-microbiological component of acute

radiation injury and modification of its development by immunotropic drugs // Medical radiology

and radiation safety. - 2016. - No. 5. – pp.39-47.

3. Konoplyannikov A.G. Cellular foundations of human radiation effects // In the book:

"Radiation medicine. Volume 1. Theoretical foundations of radiation medicine". Under the

general editorship of L.A. Ilyin. Moscow: AT Publishing House, 2004. pp.189-277.
4. Kotenko K.V., Bushmanov A.Yu., Ivanov A.A. Method of prevention and treatment of acute

radiation sickness in experiment. RF Patent 2551619. Published in Bulletin No. 15. - 05/27/2015.


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5. Mikheev A.N. Small doses of radiobiology. My little radiological faith. - Kiev,

Fotosociocenter, 2016. 371 p.
6. Nuraliev N.A., Bektimirov A.M.T., Alimova M.T., Suvonov K.J. Rules and methods of

working with laboratory animals in experimental microbiological and immunological studies //

Methodical manual. - Tashkent, 2016. - 34 p.

7. Ulanova A.M., Kuzmina T.D., Leonenko I.V. Anti-radiation properties of normal homologous

immunoglobulin in conditions of delayed use in dogs on the background of oral antibiotic therapy.

Message I. Therapeutic efficacy of normal homologous immunoglobulin // In: "Selected materials

of the Bulletin of Radiation Medicine". Volume 1" Under the general editorship of L.A. Ilyin and

A.S. Samoilov. Moscow: FMBA of the Federal State Budgetary Institution "SSC RF FMBC

named after A.I. Burnazyan", 2016. pp.663-669.
8. Tukhtaeva H.H., Nuraliev N.A., Khamdamov B.Z. Results of cytogenetic analysis of bone

marrow under chronic and acute radiation in experiment // Journal of Theoretical and Clinical

Medicine. Tashkent, 2022. No. 1. pp. 25-32.
9. Dadachova E., Casadevall A., Einstein C. Oral administration of melanin for protection against

radiation. Patent US 2014037674. 2014.
10. Ferrando M.L., Schultsz C. A hypothetical model of host-pathogen interaction of

Streptococcus suis in the gastro-intestinal tract // Gut Microbes. - 2016. - N 7(2). - P.154-162. 11.

Nuraliyev N.A., Tuxtayeva H.H. Comparative evaluation of cytogenetic changes in bone marrow

cells under chronic and acute irradiation in an experiment // Europe’s Journal of Psychology. -

2021. - № 17 (3). - P. 274-282. 12. Sender Ron, Fuchs Shai, Milo Ron. Revised Estimates for the

Number of Human and Bacteria Cells in the Body // PLOS Biology. - 2016. - Vol. 14. - Vol. 8. -

P.25-33.

Библиографические ссылки

Zharmukhamedova T.Yu., Semushina S.G., Pakhomova I.A., Pimenov M.S., Murashov A.N. International rules of work with laboratory animals during preclinical tests // Toxicological Bulletin. - Moscow, 2011. - №4(109). - P.2-9.

Ivanov A.A., Andrianova I.E., Maltsev V.N., Shalnova G.A., Stavrakova N.M., Bulynina T.M., Karaulova T.A., Bushmanov A.Yu., Ushakov I.B. Immuno-microbiological component of acute radiation injury and modification of its development by immunotropic drugs // Medical radiology and radiation safety. - 2016. - No. 5. – pp.39-47.

Konoplyannikov A.G. Cellular foundations of human radiation effects // In the book: "Radiation medicine. Volume 1. Theoretical foundations of radiation medicine". Under the general editorship of L.A. Ilyin. Moscow: AT Publishing House, 2004. pp.189-277.

Kotenko K.V., Bushmanov A.Yu., Ivanov A.A. Method of prevention and treatment of acute radiation sickness in experiment. RF Patent 2551619. Published in Bulletin No. 15. - 05/27/2015.

Mikheev A.N. Small doses of radiobiology. My little radiological faith. - Kiev, Fotosociocenter, 2016. 371 p.

Nuraliev N.A., Bektimirov A.M.T., Alimova M.T., Suvonov K.J. Rules and methods of working with laboratory animals in experimental microbiological and immunological studies // Methodical manual. - Tashkent, 2016. - 34 p.

Ulanova A.M., Kuzmina T.D., Leonenko I.V. Anti-radiation properties of normal homologous immunoglobulin in conditions of delayed use in dogs on the background of oral antibiotic therapy. Message I. Therapeutic efficacy of normal homologous immunoglobulin // In: "Selected materials of the Bulletin of Radiation Medicine". Volume 1" Under the general editorship of L.A. Ilyin and A.S. Samoilov. Moscow: FMBA of the Federal State Budgetary Institution "SSC RF FMBC named after A.I. Burnazyan", 2016. pp.663-669.

Tukhtaeva H.H., Nuraliev N.A., Khamdamov B.Z. Results of cytogenetic analysis of bone marrow under chronic and acute radiation in experiment // Journal of Theoretical and Clinical Medicine. Tashkent, 2022. No. 1. pp. 25-32.

Dadachova E., Casadevall A., Einstein C. Oral administration of melanin for protection against radiation. Patent US 2014037674. 2014.

Ferrando M.L., Schultsz C. A hypothetical model of host-pathogen interaction of Streptococcus suis in the gastro-intestinal tract // Gut Microbes. - 2016. - N 7(2). - P.154-162. 11. Nuraliyev N.A., Tuxtayeva H.H. Comparative evaluation of cytogenetic changes in bone marrow cells under chronic and acute irradiation in an experiment // Europe’s Journal of Psychology. - 2021. - № 17 (3). - P. 274-282. 12. Sender Ron, Fuchs Shai, Milo Ron. Revised Estimates for the Number of Human and Bacteria Cells in the Body // PLOS Biology. - 2016. - Vol. 14. - Vol. 8. - P.25-33.