SU1469858A1 - Method of reducing occurrence rate of spontaneous and gamma-ray induced somatic mutagenesis - Google Patents

Abstract

The invention relates to applied medicine and oncology and can be used to treat patients with a high level of spontaneous mutagenesis in somatic tissues (in some forms of malignant neoplasms, Fanconi anemia, Blum syndrome, or pigmented xeroderm), as well as therapeutic and prophylactic funds for workers in a number of occupations involving the use of mutagenic (carcinogenic) agents. To reduce the frequency of somatic mutagenesis, daily treatment of biological objects with hyperbaric oxygen (in the hyperbaric treatment system OKA-MT) with a pressure of 5 absolute atmosphere is used. The analysis of the effects of these modes of hyperbaric oxygenation on the level of somatic mutagenesis was carried out using a test system to record the frequency of somatic mosaicism in Drosophila (Drosophila. Sitnulans line with a high spontaneous level of somatic mutagenesis in the study of the antimutagenic effect and the Drosophila meloo line). -radiation dose 900 times, in the study of radioprotective action). After 2-3 sessions of hyperbaric oxygenation (each lasting 50 minutes), there is a 2-3-fold decrease in the frequency of spontaneous somatic mutations. Use 2-3. similar treatments with hyperbaric oxygen prior to irradiation of flies also result in a more than 2-fold decrease in the frequency of induced somatic mutagenesis. Thus, hyperbaric oxygenation with the treatment regimes used is a more effective antimutagenic agent than the well-known chemical antimutagenes o / -to-to-ferol and ./2-carotene with. V comparing them in the same test system. The use of the present invention may form the basis of a simple and effective method of treating a number of diseases in humans, as well as a method of protecting individuals working under the conditions of systematic exposure to mutagenic factors. 3 tab. CO 00 O1 00

Description

 The invention relates to: medicine and oncology, and can be used to treat patients with a high level of spontaneous mutagenesis in somatic tissues (in some forms of malignant tumors, anemia, anconi, Vperum syndrome, and pigmented xeroderm), as well as therapeutic and preventive - means for employees of a number of professions5 connected with the use of chugogenic (carcinogenic) agents of a physical and biological nature,

The basis of the invention is the treatment of biological objects with hyperbaric oxygen at a pressure of 1.2-1.5 absolute atmospheres. hyperbaric oxygenation is widely used in medical practice for the treatment of a number of diseases 1) of various etiologies, i As a means of anti-mutagenization; hyperbaric oxygen has not been used at present about this time |:. Taking into account that the possibility of the proposed use of therapeutic modes of hyperbaric oxygenation does not follow with evidence from the well-known characteristics of this procedure, the proposed .. || The invention should be regarded as a naming of a known method according to Yovrm's purpose.

For the analysis of antimutagenic and provectorial (with respect to spontaneously mutagenesis and induced v-F radiation) action of a hyperbaric 1 ~ system, test systems based on recording the frequency of somatic mosaicism in Drosophila were used. The antimutagenic effect of hyperbaric oxygenation was investigated on the flies of Drosophila simulans ida, protector-1C, 1st - on the fly of the species Drosophila mela-rtogaster. The treatment of flies with hyperbial oxygen was used {the period suggested by the fanier for the treatment of patients with local radiation in the acute period. Crops with Drosophila larvae, heterozygous “about recessive X -chromosomal genes, 1 were placed in a single treatment | 1T1 pressure system OKA-MT with; 2-1.5 absolute atmosphere

llflTfl i. PPT GRT1 ,. "one

Sata). In most cases, the session duration was 50 minutes, and in some sleep experiments it was increased to 3 hours.

ten

15

0

98

50

Oh with

582

daily for 2-3 days. The ejected females were viewed under a binocular stereoscopic microscope MBS-9 in incident light. Viewing led to the full departure of flies from the culture (7-8 days). The appearance of mosaic patches on the body of adults was recorded. In assessing the frequency of somatic mosaicism, the total number of first generation females viewed (F,), the number of spots and their size were taken into account. The frequency of mosaic: spots (p) in imago was calculated per 100 individuals, and then the Fisher distribution was used: (f 2 arcsin - / about 1

1 1 Woob1x

females F ,. The statistical significance of the difference between frequencies was assessed using the t-test.

Example 1, Using hyper-: baric oxygenation to obtain an antimutagenic effect. The use of the following line of Drosophila sinHl lans:

a stable line containing the recessive X chromosomal gene: Y (yellow) - yellow body and bristles and W (white) white eyes as the maternal line;

an unstable line (v, H) containing the recessive gene V (virtnilion) bright red eyes in the X chromosome, it had no significance for the written method and did not serve the purposes of the analysis) and one or two copies of the H factor of instability ( on average) per X-chromosome as the paternal line.

Cultures with heterozygous for the X-chromoson marker gene in (yellow) larvae were treated with hyperbaric oxygen using the regimens listed in Tables I and 2,

Three times the impact of hyperbaric oxygenation in the indicated regimens from the second to the fourth day of development, LICHIN01 reduces the frequency of somatic mutagenesis in carriers of one copy of the netability factor approximately twice (from 4.3% in control to 1.83% - 1.27%).

The use of hyperbaric oxygenation in the above modes reduces the frequency of mosaicism and in individuals carrying two or more copies of the instability factor (H-factor), with all the studied methods of influence, and the difference between the experimental values and

of those. in the control of statistically high level (everywhere

0.01).

Example 2. The use of hyperbaric oxygenation to obtain a radioprotective effect. In experiments, cultures of heterozygous (y + / + Sn) Droso larvae were used.

9858

On the second, third, and fourth days, the development of larvae reduces the incidence of spontaneous somatic mutagenesis in Drosophila simulans specimens carrying one, two, or more copies of the instability factor, more effective than the known antimugenic agents — al, fa-tocopherol, and beta-caro

phila melanogastor. (with low spontaneity of Roma, in contrast to these levels of somatic mutagenesis), which were subjected to the influence of hyperbolic oxygenation under the regimes indicated in the table 3. Perepreparatov hyperbaric oxygenation in therapeutic regimens reduces not only the level of spontaneous somatic mutagenesis, but also mutagen2 (the first experiment) or 20 (the second fS effect of gamma ray radiation)

experiment) hours after the last session of hyperbaric oxygenation, j «irradiation was performed. Irradiation conditions: the material was irradiated on a Raucus M apparatus with a cobalt-60 source at a distance of 1 m from the source with an irradiation field of 26–26 cm; The material is located in the center of the floor over an area of cm. Measurement of the dose is carried out in the center of the floor at the level of the material. irradiated at an exposure dose of 900 (nine hundred) happy. The measurement was carried out with a VA-I-18 dosimeter with a spherical ionization chamber calibrated in units of the exposure dose (the accuracy of the withdrawn dose + 10%).

The results of radioprotective effect of hyperbaric oxygenation in the studied modes are presented in Table. The effect of these modes of hyperbaric oxygenation before gamma irradiation (2 and 20 hours before the time of irradiation) causes a significant (more than 2 times) statistically significant high level of reduction in gamma irradiated radiation.

The application of the method of daily ans of hyperbaric oxygenadia at a pressure of 2–1.5 absolute absolute pressure as a way to reduce the frequency of spontaneous to induced

somatic mutagenesis.

Thus, the use of hyperbaric gamma irradiation of somatic oxygenation in therapeutic K / A.

mutagenesis.

 Moreover, unlike these

preparations hyperbaric oxygen-. chi in therapeutic regimens reduces not only the level of spontaneous somatic mutagenesis, but also mutagen

nor on the genetic apparatus of somatic cells.

Based on the above, it can be concluded that, in principle, it is possible to apply daily hyperbaric sessions (xigenation at a pressure of 1.2-2.5 atm to reduce the frequency of somatic mutations (spontaneous and induced - radiation) in biological objects.

The use of the present invention can be used as a basis for a simple and effective method (with the selection of the optimal duration and number of sessions for each specific case) for treating a number of diseases in humans, as well as protecting those who are systematically exposed to mutagenic factors of a physical and biological nature.

Claims (1)

Invention Formula The use of the method of daily segmentation of hyperbaric oxygenadia at a pressure of 2-1.5 absolute atmospheres as a method of reducing the frequency of spontaneous to induction -. go gamma-on K "/ TRAC. mutagenesis. IU698586 Table Reduction in the frequency of somatic mutagenesis in individuals of the genotype yw + H / ++ VH, having one copy of the H-factor, under the influence of hyperbaric oxygenation Control 805 35. T a b l i Reduction in the frequency of somatic mutagenesis in individuals of the genotype yw ++ - -H / - 4-8n vwyH, and two or more copies of the H-factor, when exposed to hyperharic oxygenation Control 1.2 absolute atmosphere for 3 min daily for 2,3 and 4 days of larva development 1.5 absolute atmosphere for 50 min daily for 2,3 and 4 days for the development of larvae .3 6.75 0.01 3, A 5.15 0.01 Reduction in the frequency of somatic mutagenesis of heterozygous larvae of y + / + n Drosophila melanogaster, caused by gamma irradiation, the preliminary effect of hyperbaric oxygenation Control Radiation in a dose of 900 is happy on the 4th day of development of the larvae from the moment of laying the eggs Hyperbaric oxygenation 1.5 of the absolute atmosphere for 50 min daily for 2.3 and 4 days of the development of the larvae. Radiation 900 glad 2 hours after the last session of hyperbaric oxygenation Irradiation at a dose of 900 glad on the fifth day of development of the larvae of the moment of egg laying P {perbaric oxygenation of 1.2 absolute atmosphere for 3 hours on days 3 and 4 of the development of the larvae. Radiation 900 happy 20 hours after the last session of hyperbaric oxygenation Table 3 14 188 66 2.46 27.00 13.30 5.83: 0.01 2l, iO. 15, 32.13 0.05