Comparison of micronuclei frequency in bone marrow cells of three rat lines

The aim of this paper is to compare the spontaneous and induced with cyclophosphamide micronucleus indexes in bone marrow cells of the Sprague Dawley, Lewis and Wistar rat lines. Five experimental groups were formed (10 animals of each sex and of each line, in every group). The first group was used...

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Опубліковано в: :Цитология и генетика
Дата:2013
Автори: Arencibia-Arrebola, D.F., Rosario-Fernandez, L.A., Suarez-Fernandez, Y.E., Vidal-Novoa, A.
Формат: Стаття
Мова:Російська
Опубліковано: Інститут клітинної біології та генетичної інженерії НАН України 2013
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Онлайн доступ:https://nasplib.isofts.kiev.ua/handle/123456789/126533
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Цитувати:Comparison of micronuclei frequency in bone marrow cells of three rat lines / D.F. Arencibia-Arrebola, L.A. Rosario-Fernandez, Y.E. Suarez-Fernandez, A. Vidal-Novoa // Цитология и генетика. — 2013. — Т. 47, № 2. — С. 70-76. — Бібліогр.: 26 назв. — англ.

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Digital Library of Periodicals of National Academy of Sciences of Ukraine
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author Arencibia-Arrebola, D.F.
Rosario-Fernandez, L.A.
Suarez-Fernandez, Y.E.
Vidal-Novoa, A.
author_facet Arencibia-Arrebola, D.F.
Rosario-Fernandez, L.A.
Suarez-Fernandez, Y.E.
Vidal-Novoa, A.
citation_txt Comparison of micronuclei frequency in bone marrow cells of three rat lines / D.F. Arencibia-Arrebola, L.A. Rosario-Fernandez, Y.E. Suarez-Fernandez, A. Vidal-Novoa // Цитология и генетика. — 2013. — Т. 47, № 2. — С. 70-76. — Бібліогр.: 26 назв. — англ.
collection DSpace DC
container_title Цитология и генетика
description The aim of this paper is to compare the spontaneous and induced with cyclophosphamide micronucleus indexes in bone marrow cells of the Sprague Dawley, Lewis and Wistar rat lines. Five experimental groups were formed (10 animals of each sex and of each line, in every group). The first group was used as the negative control (intact animals), the second one was exposed to oral administration of drugs; other conditions were the same as for the other groups. The third group was treated with 2 % Tween 65 and the fourth group was treated with 0.9 % NaCl. Both substances were administered by oral way to 2 ml/kg during 14 days. The fifth group was treated intraperitoneally with strong mutagen cyclophosphamide in the dose of 50 mg/kg (10 ml/kg in solution), on 48th and 24th hours before euthanasia. The Sprague Dawley line (both sexes) was significantly different from the other lines. Rats of this line had lower index of spontaneous formation of micronuclei, higher index of cyclophosphamide­induced micronucle formation, percent of micronucleated erythrocytes in bone marrow and the index of cytotoxicity. The results obtained make it possible to identify the most appropriate line of rats as model animals for studies of genotoxicity. It will allow also to obtain more accurate estimates of genotoxicity of various substances. Сравнивали спонтанные и индуцированные циклофосфамидом микроядерные индексы в клетках костного мозга трех линий крыс – Sprague Dawley, Льюис и Вистар. Сформировали пять экспериментальных групп (по 10 животных каждого пола и линии в каждой группе). Первую группу использовали в качестве негативного контроля (интактные животные), вторая служила контролем влияния перорального приема препаратов. Все условия содержания были одинаковыми для всех групп животных. Крыс третьей группы обрабатывали 2 % Tween 65, а четвертой группы – 0,9 % NaCl. Оба вещества вводили перорально в дозе 2 мл/кг в течение 14 дней. Животных пятой группы обрабатывали внутрибрюшинно циклофосфамидом в дозе 50 мг/кг (10 мл/кг раствора), за 48 и 24 ч до эвтаназии. Линия Sprague Dawley (оба пола) существенно отличается от других. Крысы этой линии имели низкие показатели спонтанного образования микроядер и высокий индекс при индукции циклофосфамидом, а также процент эритроцитов с микроядрами в костном мозге и индекс цитотоксичности. Полученные результаты позволяют определить наиболее подходящие линии крыс в качестве модельных животных для изучения генотоксичности. Это также позволит получать более точные оценки генотоксичности различных веществ. Порівнювали спонтанні та індуковані циклофосфамідом мікроядерні індекси в клітинах кісткового мозку трьох ліній щурів – Sprague Dawley, Люіс і Вистар. Сформували п’ять експериментальних груп (по 10 тварин кожної статі і лінії в кожній групі). Першу групу використали як негативний контроль (інтактні тварини), друга слугувала контролем впливу перорального прийому препаратів. Всі умови утримання були однаковими для всіх груп тварин. Щурів третьої групи обробляли 2 % Тween 65, а четвертої групи – 0,9 % NaCl. Обидві речовини вводили перорально в дозі 2 мл/кг впродовж 14 днів. Тварин п’ятої групи обробляли внутрішньочеревно циклофосфамідом в дозі 50 мг/кг (10 мл/кг розчину), за 48 і 24 год до евтаназії. Лінія Sprague Dawley (обидві статі) істотно відрізнялась від інших. Щури цієї лінії мали низькі показники спонтанного утворення мікроядер і високий індекс при індукції циклофосфамідом, а також відсоток еритроцитів з мікроядрами в кістковому мозку та індекс цитотоксичності. Отримані результати дозволяють визначити найбільш відповідні лінії щурів як модельних тварин для вивчення генотоксичності. Це також дозволить отримувати точніші оцінки генотоксичності різних речовин.
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fulltext 70 ISSN 0564–3783. Öèòîëîãèÿ è ãåíåòèêà. 2013. ¹ 2 D.F. ARENCIBIA-ARREBOLA 1, L.A. ROSARIO-FERNANDEZ 2, Y.E. SUAREZ-FERNANDEZ 3, A. VIDAL-NOVOA 4 1 Finlay Institute, 17 Avenue, Playa Municipality, Havana, Cuba E-mail: darencibia@finlay.edu.cu 2 Institute of Pharmacy and Food Science, Havana, Cuba 3 Medicine Veterinary Faculty UNAH, Cuba 4 Faculty of Biology, Havana University, Cuba COMPARISON OF MICRONUCLEI FREQUENCY IN BONE MARROW CELLS OF THREE RAT LINES The aim of this paper is to compare the spontane- ous and induced with cyclophosphamide micronucleus indexes in bone marrow cells of the Sprague Dawley, Lewis and Wistar rat lines. Five experimental groups were formed (10 animals of each sex and of each line, in every group). The first group was used as the nega- tive control (intact animals), the second one was exposed to oral administration of drugs; other conditions were the same as for the other groups. The third group was treated with 2 % Tween 65 and the fourth group was treated with 0.9 % NaCl. Both substances were admin- istered by oral way to 2 ml/kg during 14 days. The fifth group was treated intraperitoneally with strong mutagen cyclophosphamide in the dose of 50 mg/kg (10 ml/kg in solution), on 48th and 24th hours before euthanasia. The Sprague Dawley line (both sexes) was significantly dif- ferent from the other lines. Rats of this line had lower index of spontaneous formation of micronuclei, higher in- dex of cyclophosphamide-induced micronucle formation, percent of micronucleated erythrocytes in bone marrow and the index of cytotoxicity. The results obtained make it possible to identify the most appropriate line of rats as model animals for studies of genotoxicity. It will allow also to obtain more accurate estimates of genotoxicity of various substances. Introduction. Usually for testing genotoxicity of different substances researchers use different lines of rats. Due to genetic differences between lines their results cannot be compared. That is why the correct choosing of model organisms remains the very important problem [1]. Comparative studies of spontaneous and induced genome damages in different lines of rats could provide researchers with efficient way of choosing the most appropri- ate genetic lines of rats for their tests. One of popular test of genotoxicity is the micronucleus assay in bone marrow cells. This test is easy to perform and it provides research- ers with clear information on the rate of genome damages in bone marrow cells. This approach al- lows to register in vivo an ability of chemical sub- stances to induce chromosome breaks [2]. The increasing of frequency of polychromatic eryth- rocytes with micronuclei indicates the respective invreasing of chromosome damages [2, 3]. The detection of micronucleated erythrocytes can also be performed in species, whose spleen can- not eliminate the micronucleated erythrocytes or species sufficiently sensitive to detect agents that cause numeric or structural chromosome aberra- tions [2, 3]. The micronucleus assay must include the positive control with mutagenic substance – usually cyclophosphamide [2]. This mutagen is an alquilant agent that forms monoadducts and cross-connections between chains [3] and does not possess the specificity dependent on the cell cycle [4]. The aim of this article is to compare the spontaneous and cyclophosphamide induced micronucleus indexes of Sprague Dawley, Lewis and Wistar rat lines. Materials and methods. Animals and environ- mental conditions. Sprague Dawley, Lewis and Wistar rat lines, young adults (6–8 weeks of age) of both sexes with body mass about 180–210 g at the end of the quarantine were used in our work. They were held under temperature 23 ± 2 °C, relative humidity 60 ± 10 % and 12 h cycles of light-darkness. The access to the water and the food (CENPALAB) was ad libitum. These condi- tions were common for all groups. We adhered to the ethical principles for the investigation with laboratory animals according to the Canadian Advice of Care Animal [5]. Doses and treatment procedures. All the sub- stances were administered in the «two days» shed- ule and the concentrations were adjusted weekly according to the body mass increasing. The ani-© D.F. ARENCIBIA-ARREBOLA, L.A. ROSARIO-FERNANDEZ, Y.E. SUAREZ-FERNANDEZ, A.VIDAL-NOVOA, 2013 71 Comparison of micronuclei frequency in bone marrow cells of three rat lines ISSN 0564–3783. Öèòîëîãèÿ è ãåíåòèêà. 2013. ¹ 2 mals were randomly distributed among 5 groups with 10 rats of each sex of each line per group. The first group was used as the negative control (intact animals), the second one was exposed to oral administration of drugs (technique control group). The third experimental group was treated with 2 % Tween 65 (carrying substance 1) which is used as carrier of many nonpolar hydrophobic substances, useful as tensoactive agent [6]; the fourth group was treated with 0.9 % NaCl (carry- ing sustance 2), useful as solvent of most hydro- philic substances [7]. Both substances were pre- pared for 2 hours before using and were applied per os to 2 ml/kg during a period of 14 days. The fifth group was treated intraperitoneally with cyclophosphamide (Ledoxina®. Lemery. CORP) previously dissolved in 0,9 % NaCl, in the dose of 50 mg/kg [8]. The solution of cyclophospha- mide was used immediately after being prepared and applied to animals (in dose 10 ml/kg), on the 48th and 24th hours before euthanasia [8]. Clinical observations. We performed two daily clinical observations, during 8:30–10:30 a.m. and during 3:00–4:30 p.m. During each observation we had investigated the general clinical state of the animal, including the palpation for the detec- tion of lesions, possible breathing affectations, of the nervous, cardiovascular, gastrointestinal sys- tem, state of the skin, hair, mucous and eyes col- oration. Euthanasia method. All animals were sacrificed with ether. We provided this process in a way that the animals did not show pain signs or suffering. Bone marrow cells micronucleus assay. The mi- cronucleus assay was performed according to the modified protocol [9, 10]. One femur per animal was extracted and the medullar cavity was washed out with 3 mL of fetal bovine serum. The ob- tained cells were centrifuged at 200 g for 10 min; and the pellet was spreaded onto the slides [9]. The slides (minimum 2 slides per animal) were dried 24 h under ambient temperature, fixed in absolute methanol (5 min) and stained with 5 % Giemsa for 12–15 min [10]. The analysis was performed by three independent observers, us- ing a microscope Olympus BH-2 (100× lens with immersion). The polychromatic erythrocytes (PE) and normochromatic erythrocytes (NE) were count- ed among 2000 cells/animal. The young eryth- rocytes are the PE, microscopically they are ob- served as blue cells and the normochromatic erythrocytes (adults) are observed as pink [2, 9]. The percent of PE with micronucleus (MN-EP) was calculated in 2000 PE/animal. Later the cy- totoxicity index (PE/NE) was calculated for the total population of erythrocytes per group and total number of micronucleus (MN) [10]. In this work we presented the average results of three independent observers. Statistical analysis. We calculated the aver- age (X) and standard deviation (S.D) of studed variables. The comparisons between controls and cyclophosphamide-treated (CF) groups for the same line, among different lines, sex and ob- servers were performed with ANOVA with sig- nificance level = 0.05. The categorical variables (total number of micronuclei) were analysed by Chi-Square, with significance level of = 0.01. All the analyses were performed with STATIS- TICA (version 6) (StatSoft, Inc, 2003). Permission of ethics committee. The authors declare that this work was made on the base of good practices of preclinical laboratory that are present in the national regulation of protocols of research, approved in the Cuban republic. When this research began it was obtained the protocol approval in writing. Results and discussion. We did nît observe any systemic damages of the whole organism of animals. We did nît observe also animals with symptoms of intoxication. The damages were noted at the level of somatic cells. It let us conclude that the doses and the schedule of treatments were appropriate. The groups of ñyclophosphamide-treated ani- mals differed from other groups of rats, while groups of negative controle, groups of control of the treatment way and two solvent substances did not differe each from other in the same sex groups and lines [7, 11]. The results obtained for Sprague Dawley rats are in good accordance with our previous works [12, 13]. The low (but significant) intoxication (PE/ NE) was noted for Sprague Dawley rats of both sexes. No differences were found among sexes of the same group and rat line (Table 1) [7, 11]. In other studies differences among sexes were not observed also [14–16]. In Sprague Dawley line the PE/NE is equal 1.18 ± 0.06; the genotoxicity index was about Table 1 The cytotoxicity indexes (PE/NE) and percentage of PE with micronucleus in bone marrow of Sprague Dawley, Lewis and Wistar rats Groups n Sex MNR PE/NET MN–PE (%)T Sprague Dawley Rats Negative Control (Intact) Technique Control Vehicle Substance 1 Vehicle Substance 2 Cyclophosphamide 1 10 10 10 10 10 10 10 10 10 10 F M F M F M F M F M 28a 26a 32a 27ac 29a 30a 25a 22a 250**a 241**ac 1,21 ± 0,05 1,17 ± 0,04 1,19 ± 0,06a 1,20 ± 0,03a 1,21 ± 0,02a 1,19 ± 0,04a 1,18 ± 0,04a 1,18 ± 0,06a 0,89 ± 0,04*a 0,90 ± 0,03*a 0,20 ± 0,03a 0,18 ± 0,04a 0,22 ± 0,01a 0,19 ± 0,05a 0,20 ± 0,02a 0,21 ± 0,02a 0,17 ± 0,05a 0,15 ± 0,06a 1,74 ± 1,03*a 1,68 ± 0,92*ac Lewis Rats Negative Control (Intact) Technique Control Vehicle Substance 1 Vehicle Substance 2 Cyclophosphamide1 10 10 10 10 10 10 10 10 10 10 F M F M F M F M F M 46b 48b 48b 47b 49b 50b 42 b 44 b 295**b 291**b 1,10 ± 0,03b 1,11 ± 0,03b 1,11 ± 0,02b 1,09 ± 0,03b 1,12 ± 0,02b 1,13 ± 0,02 b 1,10 ± 0,03 b 1,13 ± 0,02 b 0,82 ± 0,02*b 0,81 ± 0,02*b 0,31 ± 0,04b 0,33 ± 0,03b 0,33 ± 0,05b 0,32 ± 0,06b 0,34 ± 0,06b 0,34 ± 0,05b 0,29 ± 0,07b 0,30 ± 0,07b 2,03 ± 1,48*b 2,00 ± 1,08*b Wistar Rats Negative Control (Intact) Technique Control Vehicle Substance 1 Vehicle Substance 2 Cyclophosphamide1 10 10 10 10 10 10 10 10 10 10 F M F M F M F M F M 53b 47bc 54b 49bc 50b 55bc 51b 46bc 292**bc 298**b 1,11 ± 0,02b 1,10 ± 0,04b 1,12 ± 0,03b 1,14 ± 0,02b 1,10 ± 0,03b 1,11 ± 0,03b 1,10 ± 0,03b 1,12 ± 0,04b 0,79 ± 0,03*b 0,80 ± 0,02*b 0,36 ± 0,03b 0,33 ± 0,02b 0,37 ± 0,02b 0,34 ± 0,04b 0,34 ± 0,05b 0,38 ± 0,03b 0,35 ± 0,03b 0,32 ± 0,05b 2,01 ± 1,56*b 2,05 ± 1,16*b Inducation. PE – Polychromatic Erythrocytes. NE – Normochromatic Erythrocytes. MN – Micronucleus. Count in 2000 cells/animal of 10 animal/group/sex/line. T Analyzed variable using the ANOVA test (X: average; SD: Standard Deviation). R Analysed variable, 2 non parametric test. 1 Intraperiytoneal treatment. *p < 0,05 (comparison with the negative control group in the same genetic line and sex, ANOVA test). **p < 0,01 (comparison with the negative control group in the same genetic line and sex, Chi Square ( 2) non parametric test). a, b – Different letters it differs when comparing among lines keeping in mind the same variable in the same experimental group and sex. c – Comparison between sexes in the same experimental group and rat lines. D.F. Arencibia-Arrebola, L.A. Rosario-Fernandez, Y.E. Suarez-Fernandez, A.Vidal-Novoa 72 ISSN 0564–3783. Öèòîëîãèÿ è ãåíåòèêà. 2013. ¹ 2 73ISSN 0564–3783. Öèòîëîãèÿ è ãåíåòèêà. 2013. ¹ 2 Comparison of micronuclei frequency in bone marrow cells of three rat lines Table 2 Variation of data obtained by three observers Groups Sex MNR PE/NET MN–PE (%)T Ob1 Ob2 Ob3 Ob1 Ob2 Ob3 Ob1 Ob2 Ob3 Sprague Dawley Rats NC TC VS1 VS2 CF F M F M F M F M F M 25a 24a 27a 22a 26a 33a 20a 20a 241a 235a 30a 24a 34a 29a 27a 30a 29b 19a 249ab 248a 29a 30a 35b 30b 34b 27a 26ab 27b 260b 240a 1,26b 1,14a 1,18a 1,22a 1,26b 1,16a 1,17a 1,15a 0,79a 0,94a 1,18a 1,19a 1,23a 1,20a 1,19a 1,20a 1,18a 1,20a 0,98a 0,77a 1,19a 1,18a 1,16a 1,19a 1,18a 1,21a 1,19a 1,19a 0,90a 0,99a 0,15a 0,22a 0,25a 0,17a 0,16a 0,22a 0,16a 0,15a 1,82b 1,55a 0,19a 0,15b 0,22a 0,19a 0,20a 0,24a 0,15a 0,13a 1,56a 1,62a 0,26a 0,17a 0,19a 0,21a 0,24a 0,17a 0,20a 0,17a 1,84a 1,87a Lewis Rats NC TC VS1 VS2 CF F M F M F M F M F M 50a 53a 43a 43a 43a 42a 40a 47a 286a 280a 43a 46a 46a 45a 55b 52ab 46a 45a 289ab 288ab 45a 45a 55a 53a 49ab 56b 40a 40a 310b 305b 1,10a 1,17b 1,08a 1,15a 1,09a 1,08a 1,12a 1,15a 0,66a 0,90b 1,13a 1,10ab 1,11a 1,07a 1,10a 1,16a 1,11a 1,14a 0,92b 0,83ab 1,07a 1,06a 1,14a 1,06a 1,17a 1,15a 1,07a 1,10a 0,88ab 0,70a 0,29ab 0,36a 0,38a 0,29a 0,34a 0,25a 0,34a 0,30a 2,09ab 2,50b 0,27a 0,34a 0,28a 0,30a 0,32a 0,38ab 0,26a 0,33a 1,76a 1,84a 0,37b 0,29a 0,34a 0,37a 0,36a 0,39b 0,27a 0,27a 2,25b 1,67a Wistar Rats NC TC VS1 VS2 CF F M F M F M F M F M 42ab 42a 55a 46a 44a 51a 49a 44a 285a 299a 50b 49a 48a 49a 56b 58a 51a 45a 296a 300a 37a 50a 59a 52a 50ab 56a 53a 49a 295a 295a 1,10a 1,07a 1,13a 1,14a 1,11a 1,10a 1,07a 1,13a 0,87b 0,83a 1,13a 1,14a 1,09a 1,17a 1,12a 1,15a 1,12a 1,16a 0,90b 0,78a 1,10a 1,09a 1,14a 1,11a 1,07a 1,08a 1,11a 1,07a 0,60a 0,80a 0,35a 0,29a 0,39a 0,34a 0,33a 0,37a 0,32a 0,33a 1,94a 2,09a 0,35a 0,37a 0,37a 0,37a 0,35a 0,36a 0,36a 0,32a 2,04a 2,00a 0,39a 0,33a 0,35a 0,32a 0,34a 0,42a 0,37a 0,31a 2,05a 2,06a Inducation. NC – Negative Control. TC – Technique Control. VS1 – Vehicle Substance 1. VS2 – Vehicle Substance 2. CF – Cyclophosphamide. O – number of observers. PE – Polychromatic Erythrocytes. NE – Normochromatic Erythrocytes. MN – Micronucleus. Count in 2000 cells/animal of 10 animal/group/sex/line. T Analyzed variable using the ANOVA test (X: average; SD: Standard Deviation, p < 0,05). RAnalyzed variable using the 2 non parametric test (p < 0,01). a, b – Different letters it differs when comparing the results of each observer in the same variable, rat line, sex and experimental group. 74 ISSN 0564–3783. Öèòîëîãèÿ è ãåíåòèêà. 2013. ¹ 2 D.F. Arencibia-Arrebola, L.A. Rosario-Fernandez, Y.E. Suarez-Fernandez, A.Vidal-Novoa 0.15 ± 0.06 % of polychromatic erythrocytes with micronucleus. The response of Sprague Daw- ley line to the ñyclophosphamide was high, but smaller than the clastogenicity results obtained in both sexes of Lewis and Wistar lines. The total MN level in Sprague Dawley rats was lower than in animals of other lines. On the other hand, the ñyclophosphamide revealed its biggest clas- togenic effect in the males of Wistar rats [11, 16]. Significant differences between sexes were not observed. The different response of rat lines on ñyclophosphamide is the result of their dif- ferences in drug metabolism [7, 17, 18]. Íepatic enzymes are fundamental in the first phase of xenobiotic metabolism that participates in the ñyclophosphamide metabolism in the liver [7, 11, 17–21]. The differences in expressions of en- zymes lead to differences in their metabolisms [20, 21]; different concentrations of the metabo- lites, active mutagene levels and so on. The comparison of data of three independent observers is shown in the Table 2. In general the results demonstrated little variation of the vari- ables and studied experimental groups. These data are in good correspondence with results of other investigators [23, 24] where high repeata- bility and consistency in their micronucleus assay in bone marrow cells were demostrated. Thus, it may be recommended to explore genotoxic ef- fects of drugs at the chromosome level [9]. Being based on the data obtained, we sup- pose that the Sprague Dawley rat line is more genetically stable than the other lines. This line revealed the lower spontaneous indexes and ac- ceptable cyclophosphamide-induced indexes [25, 26]. These results are important also due to het- erogeneity of response of the Sprague Dawley rats, similar to those in human populations [25, 26]. Futher, we suggest to use Wistar rats in ex- periments with cyclophosphamide intraperitoneal treatment as positive control. In our experiments Wistar line was the most sensitive to the muta- genic action of cyclophosphamide and this line may be good biomodel to detection of mutagenic effects of similar substances. Conclusions. The Sprague Dawley rats of both sexes differ significantly from the other lines in lower spontaneous indexes and acceptable in- duced with cyclophosphamide indexes in the bone marrow cells micronucleus assay. The authors thank to the technical personnel of the animal facilities installation from Research and Development Vicepresidency of the Finlay Institute, Cuba. D.F. Arencibia-Arrebola, L.A. Rosario-Fernandez, Y.E. Suarez-Fernandez, A. Vidal-Novoa ÑÐÀÂÍÅÍÈÅ ×ÀÑÒÎÒÛ ÌÈÊÐÎßÄÅÐ Â ÊËÅÒÊÀÕ ÊÎÑÒÍÎÃÎ ÌÎÇÃÀ ÒÐÅÕ ËÈÍÈÉ ÊÐÛÑ Ñðàâíèâàëè ñïîíòàííûå è èíäóöèðîâàííûå öèêëîôîñôàìèäîì ìèêðîÿäåðíûå èíäåêñû â êëåò- êàõ êîñòíîãî ìîçãà òðåõ ëèíèé êðûñ – Sprague Dawley, Ëüþèñ è Âèñòàð. Ñôîðìèðîâàëè ïÿòü ýêñïåðèìåíòàëüíûõ ãðóïï (ïî 10 æèâîòíûõ êàæ- äîãî ïîëà è ëèíèè â êàæäîé ãðóïïå). Ïåðâóþ ãðóï- ïó èñïîëüçîâàëè â êà÷åñòâå íåãàòèâíîãî êîíò- ðîëÿ (èíòàêòíûå æèâîòíûå), âòîðàÿ ñëóæèëà êîíò- ðîëåì âëèÿíèÿ ïåðîðàëüíîãî ïðèåìà ïðåïàðàòîâ. Âñå óñëîâèÿ ñîäåðæàíèÿ áûëè îäèíàêîâûìè äëÿ âñåõ ãðóïï æèâîòíûõ. Êðûñ òðåòüåé ãðóïïû îá- ðàáàòûâàëè 2 % Tween 65, à ÷åòâåðòîé ãðóïïû – 0,9 % NaCl. Îáà âåùåñòâà ââîäèëè ïåðîðàëüíî â äîçå 2 ìë/êã â òå÷åíèå 14 äíåé. Æèâîòíûõ ïÿ- òîé ãðóïïû îáðàáàòûâàëè âíóòðèáðþøèííî öèêëî- ôîñôàìèäîì â äîçå 50 ìã/êã (10 ìë/êã ðàñòâîðà), çà 48 è 24 ÷ äî ýâòàíàçèè. Ëèíèÿ Sprague Dawley (îáà ïîëà) ñóùåñòâåííî îòëè÷àåòñÿ îò äðóãèõ. Êðûñû ýòîé ëèíèè èìåëè íèçêèå ïîêàçàòåëè ñïîíòàííîãî îáðàçîâàíèÿ ìèêðîÿäåð è âûñîêèé èíäåêñ ïðè èíäóêöèè öèêëîôîñôàìèäîì, à òàêæå ïðîöåíò ýðèòðîöèòîâ ñ ìèêðîÿäðàìè â êîñòíîì ìîçãå è èíäåêñ öèòîòîêñè÷íîñòè. Ïîëó÷åííûå ðå- çóëüòàòû ïîçâîëÿþò îïðåäåëèòü íàèáîëåå ïîäõî- äÿùèå ëèíèè êðûñ â êà÷åñòâå ìîäåëüíûõ æè- âîòíûõ äëÿ èçó÷åíèÿ ãåíîòîêñè÷íîñòè. Ýòî òàêæå ïîçâîëèò ïîëó÷àòü áîëåå òî÷íûå îöåíêè ãåíîòîê- ñè÷íîñòè ðàçëè÷íûõ âåùåñòâ. D.F. Arencibia-Arrebola, L.A. Rosario-Fernandez, Y.E. Suarez-Fernandez, A. Vidal-Novoa ÏÎвÂÍßÍÍß ×ÀÑÒÎÒÈ Ì²ÊÐÎßÄÅÐ Â Ê˲ÒÈÍÀÕ Ê²ÑÒÊÎÂÎÃÎ ÌÎÇÊÓ ÒÐÜÎÕ Ë²Í²É ÙÓв Ïîð³âíþâàëè ñïîíòàíí³ òà ³íäóêîâàí³ öèêëî- ôîñôàì³äîì ì³êðîÿäåðí³ ³íäåêñè â êë³òèíàõ ê³ñò- êîâîãî ìîçêó òðüîõ ë³í³é ùóð³â – Sprague Daw- ley, Ëþ³ñ ³ Âèñòàð. Ñôîðìóâàëè ï’ÿòü åêñïåðè- ìåíòàëüíèõ ãðóï (ïî 10 òâàðèí êîæíî¿ ñòàò³ ³ ë³í³¿ â êîæí³é ãðóï³). Ïåðøó ãðóïó âèêîðèñòàëè ÿê íåãàòèâíèé êîíòðîëü (³íòàêòí³ òâàðèíè), äðóãà ñëóãóâàëà êîíòðîëåì âïëèâó ïåðîðàëüíîãî ïðè- éîìó ïðåïàðàò³â. Âñ³ óìîâè óòðèìàííÿ áóëè îäíà- êîâèìè äëÿ âñ³õ ãðóï òâàðèí. Ùóð³â òðåòüî¿ ãðóïè 75 Comparison of micronuclei frequency in bone marrow cells of three rat lines ISSN 0564–3783. Öèòîëîãèÿ è ãåíåòèêà. 2013. ¹ 2 îáðîáëÿëè 2 % Òween 65, à ÷åòâåðòî¿ ãðóïè – 0,9 % NaCl. Îáèäâ³ ðå÷îâèíè ââîäèëè ïåðîðàëüíî â äîç³ 2 ìë/êã âïðîäîâæ 14 äí³â. Òâàðèí ï’ÿòî¿ ãðóïè îáðîáëÿëè âíóòð³øíüî÷åðåâíî öèêëîôîñôàì³äîì â äîç³ 50 ìã/êã (10 ìë/êã ðîç÷èíó), çà 48 ³ 24 ãîä äî åâòàíà糿. ˳í³ÿ Sprague Dawley (îáèäâ³ ñòàò³) ³ñòîò- íî â³äð³çíÿëàñü â³ä ³íøèõ. Ùóðè ö³º¿ ë³í³¿ ìàëè íèçüê³ ïîêàçíèêè ñïîíòàííîãî óòâîðåííÿ ì³êðî- ÿäåð ³ âèñîêèé ³íäåêñ ïðè ³íäóêö³¿ öèêëîôîñ- ôàì³äîì, à òàêîæ â³äñîòîê åðèòðîöèò³â ç ì³êðî- ÿäðàìè â ê³ñòêîâîìó ìîçêó òà ³íäåêñ öèòîòîê- ñè÷íîñò³. Îòðèìàí³ ðåçóëüòàòè äîçâîëÿþòü âèçíà- ÷èòè íàéá³ëüø â³äïîâ³äí³ ë³í³¿ ùóð³â ÿê ìîäåëüíèõ òâàðèí äëÿ âèâ÷åííÿ ãåíîòîêñè÷íîñò³. Öå òàêîæ äîçâîëèòü îòðèìóâàòè òî÷í³ø³ îö³íêè ãåíîòîêñè÷- íîñò³ ð³çíèõ ðå÷îâèí. REFERENCES 1. Arencibia D.F., Rosario L.A., Suárez Y.E., Vidal A. Letter to the Editor: Assessment and comparison between three lines of rats in four genotoxicity assay. Retel 2011; 35(2):16–24. 2. OECD. Genetic Toxicology: In vivo Mammalian Erythrocyte Micronucleus Test, in bone marrow cells TG 474 (Annual Report 2009). Public Affairs and Communications Directorate Editions. Paris. France: OECD online Bookshop Editions. 2009. p. 7–123. Available in: http://www.oecd.org/ bookshop 3. Yiqiang L., Mengmeng Q., Liwei S., Yulin W., Yuan- gao C.H. 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id nasplib_isofts_kiev_ua-123456789-126533
institution Digital Library of Periodicals of National Academy of Sciences of Ukraine
issn 0564-3783
language Russian
last_indexed 2025-12-07T16:26:18Z
publishDate 2013
publisher Інститут клітинної біології та генетичної інженерії НАН України
record_format dspace
spelling Arencibia-Arrebola, D.F.
Rosario-Fernandez, L.A.
Suarez-Fernandez, Y.E.
Vidal-Novoa, A.
2017-11-25T19:26:06Z
2017-11-25T19:26:06Z
2013
Comparison of micronuclei frequency in bone marrow cells of three rat lines / D.F. Arencibia-Arrebola, L.A. Rosario-Fernandez, Y.E. Suarez-Fernandez, A. Vidal-Novoa // Цитология и генетика. — 2013. — Т. 47, № 2. — С. 70-76. — Бібліогр.: 26 назв. — англ.
0564-3783
DOI: 10.3103/S0095452713020023
https://nasplib.isofts.kiev.ua/handle/123456789/126533
The aim of this paper is to compare the spontaneous and induced with cyclophosphamide micronucleus indexes in bone marrow cells of the Sprague Dawley, Lewis and Wistar rat lines. Five experimental groups were formed (10 animals of each sex and of each line, in every group). The first group was used as the negative control (intact animals), the second one was exposed to oral administration of drugs; other conditions were the same as for the other groups. The third group was treated with 2 % Tween 65 and the fourth group was treated with 0.9 % NaCl. Both substances were administered by oral way to 2 ml/kg during 14 days. The fifth group was treated intraperitoneally with strong mutagen cyclophosphamide in the dose of 50 mg/kg (10 ml/kg in solution), on 48th and 24th hours before euthanasia. The Sprague Dawley line (both sexes) was significantly different from the other lines. Rats of this line had lower index of spontaneous formation of micronuclei, higher index of cyclophosphamide­induced micronucle formation, percent of micronucleated erythrocytes in bone marrow and the index of cytotoxicity. The results obtained make it possible to identify the most appropriate line of rats as model animals for studies of genotoxicity. It will allow also to obtain more accurate estimates of genotoxicity of various substances.
Сравнивали спонтанные и индуцированные циклофосфамидом микроядерные индексы в клетках костного мозга трех линий крыс – Sprague Dawley, Льюис и Вистар. Сформировали пять экспериментальных групп (по 10 животных каждого пола и линии в каждой группе). Первую группу использовали в качестве негативного контроля (интактные животные), вторая служила контролем влияния перорального приема препаратов. Все условия содержания были одинаковыми для всех групп животных. Крыс третьей группы обрабатывали 2 % Tween 65, а четвертой группы – 0,9 % NaCl. Оба вещества вводили перорально в дозе 2 мл/кг в течение 14 дней. Животных пятой группы обрабатывали внутрибрюшинно циклофосфамидом в дозе 50 мг/кг (10 мл/кг раствора), за 48 и 24 ч до эвтаназии. Линия Sprague Dawley (оба пола) существенно отличается от других. Крысы этой линии имели низкие показатели спонтанного образования микроядер и высокий индекс при индукции циклофосфамидом, а также процент эритроцитов с микроядрами в костном мозге и индекс цитотоксичности. Полученные результаты позволяют определить наиболее подходящие линии крыс в качестве модельных животных для изучения генотоксичности. Это также позволит получать более точные оценки генотоксичности различных веществ. Порівнювали спонтанні та індуковані циклофосфамідом мікроядерні індекси в клітинах кісткового мозку трьох ліній щурів – Sprague Dawley, Люіс і Вистар.
Сформували п’ять експериментальних груп (по 10 тварин кожної статі і лінії в кожній групі). Першу групу використали як негативний контроль (інтактні тварини), друга слугувала контролем впливу перорального прийому препаратів. Всі умови утримання були однаковими для всіх груп тварин. Щурів третьої групи обробляли 2 % Тween 65, а четвертої групи – 0,9 % NaCl. Обидві речовини вводили перорально в дозі 2 мл/кг впродовж 14 днів. Тварин п’ятої групи обробляли внутрішньочеревно циклофосфамідом в дозі 50 мг/кг (10 мл/кг розчину), за 48 і 24 год до евтаназії. Лінія Sprague Dawley (обидві статі) істотно відрізнялась від інших. Щури цієї лінії мали низькі показники спонтанного утворення мікроядер і високий індекс при індукції циклофосфамідом, а також відсоток еритроцитів з мікроядрами в кістковому мозку та індекс цитотоксичності. Отримані результати дозволяють визначити найбільш відповідні лінії щурів як модельних тварин для вивчення генотоксичності. Це також дозволить отримувати точніші оцінки генотоксичності різних речовин.
The authors thank to the technical personnel of the animal facilities installation from Research and Development Vicepresidency of the Finlay Institute, Cuba.
ru
Інститут клітинної біології та генетичної інженерії НАН України
Цитология и генетика
Оригинальные работы
Comparison of micronuclei frequency in bone marrow cells of three rat lines
Сравнение частоты микроядер в клетках костного мозга трех линий крыс
Порівняння частоти мікроядер в клітинах кісткового мозку трьох ліній щурів
Article
published earlier
spellingShingle Comparison of micronuclei frequency in bone marrow cells of three rat lines
Arencibia-Arrebola, D.F.
Rosario-Fernandez, L.A.
Suarez-Fernandez, Y.E.
Vidal-Novoa, A.
Оригинальные работы
title Comparison of micronuclei frequency in bone marrow cells of three rat lines
title_alt Сравнение частоты микроядер в клетках костного мозга трех линий крыс
Порівняння частоти мікроядер в клітинах кісткового мозку трьох ліній щурів
title_full Comparison of micronuclei frequency in bone marrow cells of three rat lines
title_fullStr Comparison of micronuclei frequency in bone marrow cells of three rat lines
title_full_unstemmed Comparison of micronuclei frequency in bone marrow cells of three rat lines
title_short Comparison of micronuclei frequency in bone marrow cells of three rat lines
title_sort comparison of micronuclei frequency in bone marrow cells of three rat lines
topic Оригинальные работы
topic_facet Оригинальные работы
url https://nasplib.isofts.kiev.ua/handle/123456789/126533
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