natgillin/translations-raw huggingface dataset:
This method is a replicate of the OECD TG 474, Mammalian Erythrocyte Micronucleus Test (1997).
Ta metoda ustreza metodi OECD TG 474, Mammalian Erythrocyte Micronucleus Test (1997).
The mammalian in vivo micronucleus test is used for the detection of damage induced by the test substance to the chromosomes or the mitotic apparatus of erythroblasts by analysis of erythrocytes as sampled in bone marrow and/or peripheral blood cells of animals, usually rodents.
Preizkus mikronukleusov in vivo pri sesalcih se uporablja za odkrivanje poškodb, ki jih preizkušana snov povzroči na kromosomih ali mitotičnem aparatu eritroblastov, z analizo eritrocitov, vzorčenih iz kostnega mozga in/ali celic periferne krvi živali, navadno glodavcev.
The purpose of the micronucleus test is to identify substances that cause cytogenetic damage, which results in the formation of micronuclei containing lagging chromosome fragments or whole chromosomes.
Namen preizkusa mikronukleusov je določiti snovi, povzročiteljice citogenetskih poškodb, zaradi katerih nastanejo mikronukleusi, ki vsebujejo zaostale fragmente kromosomov ali cele kromosome.
When a bone marrow erythroblast develops into a polychromatic erythrocyte, the main nucleus is extruded; any micronucleus that has been formed may remain behind in the otherwise anucleated cytoplasm.
Ko se eritroblast iz kostnega mozga razvije v polikromatični eritrocit, se jedro izvrže; kakršen koli mikronukleus, kije nastal, lahko ostane v drugače brezjedrni citoplazmi.
Visualisation of micronuclei is facilitated in these cells because they lack a main nucleus.
Vidnost mikronukleusov je v teh celicah olajšana, ker nimajo jedra.
An increase in the frequency of micronucleated polychromatic erythrocytes in treated animals is an indication of induced chromosome damage.
Povečanje pogostnosti polikromatičnih eritrocitov z mikronukleusi pri tretiranih živalih je znak induciranih poškodb kromosomov.
The bone marrow of rodents is routinely used in this test since polychromatic erythrocytes are produced in that tissue.
Pri tem preizkusu se redno uporablja kostni mozeg glodavcev, saj v tem tkivu nastajajo polikromatični eritrociti.
The measurement of micronucleated immature (polychromatic) erythrocytes in peripheral blood is equally acceptable in any species in which the inability of the spleen to remove micronucleated erythrocytes has been demonstrated, or which has shown an adequate sensitivity to detect agents that cause structural or numerical chromosome aberrations.
Določanje nezrelih (polikromatičnih) eritrocitov z mikronukleusi v periferni krvi je enako sprejemljivo pri kateri koli vrsti, pri kateri je bilo dokazano, da vranica ni zmožna odstraniti eritrocitov z mikronukleusi, ali ki je pokazala dovoljšno občutljivost za zaznavanje snovi, povzročajočih strukturne ali numerične kromosomske aberacije.
Micronuclei can be distinguished by a number of criteria.
Mikronukleusi se lahko razločijo na podlagi številnih meril.
These include identification of the presence or absence of a kinetochore or centromeric DNA in the micronuclei.
Ta vključujejo določanje navzočnosti ali odsotnosti kinetohora ali centromerne DNA v mikronukleusih.
The frequency of micronucleated immature (polychromatic) erythrocytes is the principal endpoint.
Pogostnost nezrelih (polikromatičnih) eritrocitov z mikronukleusi je glavna končna točka.
The number of mature (normochromatic) erythrocytes in the peripheral blood that contain micronuclei among a given number of mature erythrocytes can also be used as the endpoint of the assay when animals are treated continuously for four weeks or more.
Število zrelih (normokromatičnih) eritrocitov, ki vsebujejo mikronukleuse, v periferni krvi med določenim številom zrelih eritrocitov se tudi lahko uporabi kot končna točka preizkusa, kadar se živali tretirajo štiri tedne ali več.
This mammalian in vivo micronucleus test is especially relevant to assessing mutagenic hazard in that it allows consideration of factors of in vivo metabolism, pharmacokinetics and DNA-repair processes although these may vary among species, among tissues and among genetic endpoints.
Ta preizkus mikronukleusov in vivo pri sesalcih je posebno primeren za ocenjevanje nevarnosti mutagenosti, ker omogoča upoštevanje dejavnikov presnove in vivo, farmakokinetike in popravljanja DNA, čeprav so ti lahko različni pri različnih vrstah, tkivih in genetskih končnih točkah.
An in vivo assay is also useful for further investigation of a mutagenic effect detected by an in vitro system.
Preizkus in vivo je koristen tudi za nadaljnjo preiskavo mutagenih učinkov, odkritih v sistemu in vitro.
Centromere (Kinetochore): region(s) of a chromosome with which spindle fibers are associated during cell division, allowing orderly movement of daughter chromosomes to the poles of the daughter cells.
Centromera (kinetohor): del(-i) kromosoma, s katerim(-i) se med celično delitvijo povežejo niti delitvenega vretena, kar omogoči urejeno gibanje hčerinskih kromosomov proti poloma hčerinskih celic.
Micronuclei: small nuclei, separate from and additional to the main nuclei of cells, produced during telophase of mitosis (meiosis) by lagging chromosome fragments or whole chromosomes.
Mikronukleusi: majhna jedra, poleg glavnega jedra celic in ločena od njega, ki nastanejo med telofazo mitoze (mejoze) iz zaostalih fragmentov kromosomov ali celih kromosomov.
Normochromatic erythrocyte: mature erythrocyte that lacks ribosomes and can be distinguished from immature, polychromatic erythrocytes by stains selective for ribosomes.
Normokromatični eritrocit: zreli eritrocit, ki nima ribosomov in ga lahko ločimo od nezrelih, polikromatičnih eritrocitov z barvanjem, selektivnim za ribosome.
Polychromatic erythrocyte: immature erythrocyte, in an intermediate stage of development, that still contains ribosomes and therefore can be distinguished from mature, normochromatic erythrocytes by stains selective for ribosomes.
Polikromatični eritrocit: nezreli eritrocit, v vmesnem stadiju razvoja, ki še vedno vsebuje ribosome in ga zato lahko ločimo od zrelih, normokromatičnih eritrocitov z barvanjem, selektivnim za ribosome.
Animals are exposed to the test substance by an appropriate route.
Živali se primerno izpostavijo preizkušam snovi.
If bone marrow is used, the animals are sacrificed at appropriate times after treatment, the bone marrow extracted, and preparations made and stained (1)(2)(3)(4)(5)(6)(7).
Če se uporabi kostni mozeg, se živali žrtvujejo ob primernih časih po tretiranju, nato se odvzame kostni mozeg ter se pripravijo in obarvajo preparati (1) (2) (3) (4) (5) (6) (7).
When peripheral blood is used, the blood is collected at appropriate times after treatment and smear preparations are made and stained (4)(8)(9)(10).
Kadar se uporabi periferna kri, se kri odvzame ob primernih časih po tretiranju, nato se pripravijo in obarvajo razmazi krvi (4) (8) (9) (10).
For studies with peripheral blood, as little time as possible should elapse between the last exposure and cell harvest.
Pri študijah s periferno krvjo naj med zadnjo izpostavitvijo in odvzemom celic preteče čimmanj časa.
Preparations are analysed for the presence of micronuclei.
Preparati se analizirajo, da se določi navzočnost mikronukleusov.
Mice or rats are recommended if bone marrow is used, although any appropriate mammalian species may be used.
Če se uporabi kostni mozeg, se priporočajo miši ali podgane, lahko pa se uporabi katera koli primerna vrsta sesalcev.
When peripheral blood is used, mice are recommended.
Kadar se uporabi periferna kri, se priporočajo miši.
However, any appropriate mammalian species may be used provided it is a species in which the spleen does not remove micronucleated erythrocytes or a species, which has shown an adequate sensitivity to detect agents that cause structural or numerical chromosome aberrations.
Lahko pa se uporabi katera koli primerna vrsta sesalcev, pri kateri vranica ne odstrani eritrocitov z mikronukleusi ali ki je pokazala dovoljšno občutljivost za zaznavanje snovi, povzročajočih strukturne ali numerične kromosomske aberacije.
At the commencement of the study, the weight variation of animals should be minimal and not exceed ±20 % of the mean weight of each sex.
Ob začetku študije naj bo nihanje teže živali čim manjše in naj ne presega ± 20 % srednje vrednosti teže vsakega spola.
If other than well-known solvents/vehicles are used, their inclusion should be supported with reference data indicating their compatibility.
Če se uporabijo manj poznana topila/nosilci, naj njihovo vključitev podpirajo referenčni podatki, ki kažejo na njihovo združljivost.
Except for treatment with the test substance, animals in the control groups should be handled in an identical manner to animals of the treatment groups.
Razen tretiranja s preizkušano snovjo naj se z živalmi v kontrolnih skupinah ravna enako kakor s tistimi v tretiranih skupinah.
Positive controls should produce micronuclei in vivo at exposure levels expected to give a detectable increase over background.
Snovi pozitivne kontrole naj pri ravneh izpostavljenosti, pri katerih se pričakuje zaznavno povečanje glede na ozadje, povzročijo nastanek mikronukleusov in vivo.
In addition, the use of chemical class-related positive control chemicals may be considered, when available.
Poleg tega se lahko uporabijo kemikalije pozitivne kontrole, ki sodijo v isto skupino nevarnosti kakor preizkušana kemikalija, kadar so na voljo.
N-ethyl-N-nitrosourea
N-etil-N-nitrozosecnina
Negative controls, treated with solvent or vehicle alone, and otherwise treated in the same way as the treatment groups should be included for every sampling time, unless acceptable inter-animal variability and frequencies of cells with micronuclei are demonstrated by historical control data.
Negativni kontrolni vzorci, tretirani le s topilom ali nosilcem, drugače pa obravnavani enako kakor tretirane skupine, naj se vključijo v vsako vzorčenje, razen če pretekli kontrolni podatki dokazujejo sprejemljivo spremenljivost med posameznimi živalmi in pogostnost celic z mikronukleusi.
If peripheral blood is used, a pre-treatment sample may also be acceptable as a concurrent negative control, but only in the short peripheral blood studies (e.g. 1-3 treatment(s)) when the resulting data are in the expected range for the historical control.
Če se uporabi periferna kri, je kot negativni kontrolni vzorec lahko sprejemljiv tudi vzorec pred tretiranjem, vendar le pri kratkotrajnih študijah periferne krvi (npr. 1-3 tretiranje(-a)), kadar so dobljeni podatki v pričakovanem območju glede na preteklo kontrolo.
Each treated and control group must include at least five analysable animals per sex (11).
Vsaka tretirana in kontrolna skupina mora vključevati vsaj pet živali vsakega spola, ki jih je mogoče analizirati (11).
If at the time of the study there are data available from studies in the same species and using the same route of exposure that demonstrate that there are no substantial differences between sexes in toxicity, then testing in a single sex will be sufficient.
Če so v času študije na voljo podatki študij o isti vrsti in ob uporabi istega načina izpostavljanja, ki dokazujejo, da med spoloma ni znatnih razlik v toksičnosti, bo zadostovalo preizkušanje na enem spolu.
No standard treatment schedule (i.e. one, two or more treatments at 24 h intervals) can be recommended.
Ni mogoče priporočiti nobenega standardnega programa tretiranja (to je enega, dveh ali več vnosov v 24-urnih intervalih).
The samples from extended dose regimens are acceptable as long as a positive effect has been demonstrated for this study or, for a negative study, as long as toxicity has been demonstrated or the limit dose has been used, and dosing continued until the time of sampling.
Vzorci iz dolgotrajnih režimov odmerjanja so sprejemljivi, pod pogojem, daje bil dokazan pozitivni učinek pri tej študiji ali pri negativni študiji, če je bila dokazana toksičnost ali je bil uporabljen mejni odmerek in se je odmerjanje nadaljevalo do vzorčenja.
Test substances may also be administered as a split dose, i.e., two treatments on the same day separated by no more than a few hours, to facilitate administering a large volume of material.
Preizkušane snovi se lahko dajejo tudi v razdeljenem odmerku, to pomeni dva vnosa v istem dnevu, ne več kakor nekaj ur narazen, da se olajša dajanje velikega volumna materiala.
The test may be performed in two ways:
Preizkus se lahko izvede na dva načina:
animals are treated with the test substance once.
živali se s snovjo tretirajo enkrat.
Samples of bone marrow are taken at least twice, starting not earlier than 24 hours after treatment, but not extending beyond 48 hours after treatment with appropriate intervals between samples.
Vzorci kostnega mozga se odvzamejo vsaj dvakrat, vsaj 24 ur po tretiranju in najpozneje 48 ur po tretiranju, z ustreznimi intervali med vzorčenji.
The use of sampling times earlier than 24 hours after treatment should be justified.
Vzorčenje manj kakor 24 ur po tretiranju naj se utemelji.
Samples of peripheral blood are taken at least twice, starting not earlier than 36 hours after treatment, with appropriate intervals following the first sample, but not extending beyond 72 hours.
Vzorci periferne krvi se odvzamejo vsaj dvakrat, vsaj 36 ur po tretiranju in najpozneje 72 ur po tretiranju, z ustreznimi intervali med vzorčenji.
When a positive response is recognised at one sampling time, additional sampling is not required.
Ko se pri posameznem vzorčenju opazi pozitivni odziv, dodatno vzorčenje ni potrebno;
if two or more daily treatments are used (e.g. two or more treatments at 24 hour intervals), samples should be collected once between 18 and 24 hours following the final treatment for the bone marrow and once between 36 and 48 hours following the final treatment for the peripheral blood (12);
če se opravita dva dnevna vnosa ali več (npr. dva vnosa ali več v 24-urnih intervalih), se vzorci odvzamejo enkrat med 18. in 24. uro po zadnjem vnosu pri kostnem mozgu in enkrat med 36. in 48. uro po zadnjem vnosu pri periferni krvi (12).
Other sampling times may be used in addition, when relevant.
Lahko se vzamejo dodatni vzorci ob drugih časih, kadar je to primerno.
If a range finding study is performed because there are no suitable data available, it should be performed in the same laboratory, using the same species, strain, sex, and treatment regimen to be used in the main study (13).
Če se opravi študija za ugotavljanje območja, ker ni na voljo ustreznih podatkov, naj se opravi v istem laboratoriju, na isti vrsti, sevu in spolu ob enakem režimu tretiranja, kakor bo to uporabljeno v glavni študiji (13).
The highest dose may also be defined as a dose that produces some indication of toxicity in the bone marrow (e.g. a reduction in the proportion of immature erythrocytes among total erythrocytes in the bone marrow or peripheral blood).
Največji odmerek se lahko opredeli tudi kot odmerek, ki povzroči nekaj znakov toksičnosti v kostnem mozgu (npr. zmanjšanje deleža nezrelih eritrocitov med vsemi eritrociti v kostnem mozgu ali periferni krvi).
If a test at one dose level of at least 2000 mg/kg body weight using a single treatment, or as two treatments on the same day, produces no observable toxic effects, and if genotoxicity would not be expected based upon data from structurally related substances, then a full study using three dose levels may not be considered necessary.
Če preizkus pri eni velikosti odmerka vsaj 2000 mg/kg telesne teže, ki se da v enem vnosu ali dveh vnosih v istem dnevu, ne povzroči nobenih opaznih toksičnih učinkov in če se na podlagi podatkov o strukturno sorodnih snoveh ne pričakuje, da bo snov genotksična, se lahko pojmuje, da popolna študija z uporabo treh velikosti odmerkov ni potrebna.
Bone marrow/blood preparation
Priprava kostnega mozga/krvi
Bone marrow cells are usually obtained from the femurs or tibias immediately following sacrifice.
Celice kostnega mozga se navadno odvzamejo iz stegnenic ali golenic takoj po žrtvovanju.
Commonly, cells are removed from femurs or tibias, prepared and stained using established methods.
Navadno se celice odstranijo iz stegnenic ali golenic, se preparirajo in obarvajo z uporabo uveljavljenih metod.
Peripheral blood is obtained from the tail vein or other appropriate blood vessel.
Periferna kri se odvzame iz repne vene ali druge primerne krvne žile.
Blood cells are immediately stained supravitally (8)(9)(10) or smear preparations are made and then stained.
Krvne celice se takoj supravitalno obarvajo (8) (9) (10) ali pa se pripravijo razmazi, ki se nato obarvajo.
The use of a DNA specific stain (e.g. acridine orange (14) or Hoechst 33258 plus pyronin-Y (15)) can eliminate some of the artifacts associated with using a non DNA specific stain.
Uporaba DNA-specifičnega barvila (npr. akridin oranž (14) ali Hoechst 33258 plus pyronin-Y (15)) lahko prepreči nastanek nekaterih artefaktov, povezanih z uporabo barvila, ki ni specifično za DNA.
This advantage does not preclude the use of conventional stains (e.g. Giemsa).
Ta prednost ne preprečuje uporabe splošno uporabljenih barvil (npr. Giemsa).
Additional systems (e.g. cellulose columns to remove nucleated cells (16)) can also be used provided that these systems have been shown to adequately work for micronucleus preparation in the laboratory.
Lahko se uporabijo tudi dodatni sistemi (npr. celulozne kolone za odstranitev celic z jedri (16)), pod pogojem, daje bilo dokazano, da ti sistemi zadovoljivo delujejo pri pripravi mikronukleusov v laboratoriju.
The proportion of immature among total (immature + mature) erythrocytes is determined for each animal by counting a total of at least 200 erythrocytes for bone marrow and 1000 erythrocytes for peripheral blood (17).
Za vsako žival se določi delež nezrelih med vsemi (nezrelimi + zrelimi) eritrociti, tako da se prešteje skupaj vsaj 200 eritrocitov pri kostnem mozgu in 1000 eritrocitov pri periferni krvi (17).
At least 2000 immature erythrocytes per animal are scored for the incidence of micronucleated immature erythrocytes.
V določanje incidence nezrelih eritrocitov z mikronukleusi se vključi vsaj 2000 nezrelih eritrocitov na žival.
Additional information may be obtained by scoring mature erythrocytes for micronuclei.
Dodatne informacije se lahko pridobijo s štetjem zrelih eritrocitov z mikronukleusi.
When analysing slides, the proportion of immature erythrocytes among total erythrocytes should not be less than 20 % of the control value.
Pri analizi mikroskopskih preparatov naj delež nezrelih eritrocitov med vsemi eritrociti ne bo manjši od 20 % kontrolne vrednosti.
When animals are treated continuously for four weeks or more, at least 2000 mature erythrocytes per animal can also be scored for the incidence of micronuclei.
Kadar se živali tretirajo nepretrgano štiri tedne ali več, se lahko določi tudi incidenca mikronukleusov v vsaj 2000 zrelih eritrocitih na žival.
Systems for automated analysis (image analysis and cell suspensions flow cytometry) are acceptable alternatives to manual evaluation if appropriately justified and validated.
Sistemi za avtomatizirano analizo (slikovna analiza in pretočna citometrična analiza celičnih suspenzij) so sprejemljiva alternativa ročnemu določanju, če so ustrezno utemeljeni in validirani.
The number of immature erythrocytes scored, the number of micronucleated immature erythrocytes, and the number of immature among total erythrocytes should be listed separately for each animal analysed.
Za vsako analizirano žival posebej naj se navedejo število štetih nezrelih eritrocitov, število nezrelih eritrocitov z mikronukleusi in število nezrelih med vsemi eritrociti.
When animals are treated continuously for four weeks or more, the data on mature erythrocytes should also be given if it is collected.
Kadar se živali tretirajo nepretrgano štiri tedne ali več, se navedejo tudi podatki o zrelih eritrocitih, če so bili zbrani.
The proportion of immature among total erythrocytes and, if considered applicable, the percentage of micronucleated erythrocytes is given for each animal.
Za vsako žival se navede delež nezrelih med vsemi eritrociti, in če je to primerno, odstotek eritrocitov z mikronukleusi.
There are several criteria for determining a positive result, such as a dose-related increase in the number of micronucleated cells or a clear increase in the number of micronucleated cells in a single dose group at a single sampling time.
Pozitivni rezultat se lahko določi na podlagi številnih meril, kakor je na primer z odmerkom povezano povečanje števila celic z mikronukleusi ali jasno povečanje števila celic z mikronukleusi v posamezni tretirani skupini ob posameznem vzorčenju.
Statistical methods may be used as an aid in evaluating the test results (18)(19).
Pri vrednotenju rezultatov preizkusa se kot pomoč lahko uporabijo statistične metode (18) (19).
Positive results in the micronucleus test indicate that the substance induces micronuclei which are the result of chromosomal damage or damage to the mitotic apparatus in the erythroblasts of the test species.
Pozitivni rezultati preizkusa mikronukleusov pomenijo, da snov povzroča nastanek mikronukleusov, ki so posledica poškodb kromosomov ali mitotičnega aparata v eritroblastih preizkusne vrste.
Negative results indicate that, under the test conditions, the test substance does not produce micronuclei in the immature erythrocytes of the test species.
Negativni rezultati pomenijo, da preizkušana snov pri preizkusnih pogojih ne povzroča nastanka mikronukelusov v nezrelih eritrocitih preizkusne vrste.
individual weight of the animals at the start of the test, including body weight range, mean and standard deviation for each group.
teža posameznih živali na začetku preizkusa, skupaj z območjem telesne teže, srednjo vrednostjo in standardnim odklonom za vsako skupino.
positive and negative (vehicle/solvent) control data,
podatki o pozitivnih in negativnih (nosilec/topilo) kontrolnih vzorcih,
criteria for scoring micronucleated immature erythrocytes,
merila za štetje nezrelih eritrocitov z mikronukleusi,
proportion of immature erythrocytes among total erythrocytes,
delež nezrelih eritrocitov med vsemi eritrociti,
number of micronucleated immature erythrocytes, given separately for each animal,
število nezrelih eritrocitov z mikronukleusi, navedeno za vsako žival posebej,
mean ± standard deviation of micronucleated immature erythrocytes per group,
srednja vrednost ± standardni odklon nezrelih eritrocitov z mikronukleusi na skupino,
statistical analyses and methods applied,
uporabljene statistične analize in metode,
concurrent and historical negative control data,
podatki o sočasni in pretekli negativni kontroli,
Heddle, J.A., (1973) A Rapid In Vivo Test for Chromosomal Damage, Mutation Res., 18, p. 187-190.
Heddle, J. A. (1973), A Rapid In Vivo Test for Chromosomal Damage, Mutation Res., 18, str. 187–190.
Schmid, W., (1975) The Micronucleus Test, Mutation Res., 31, p. 9-15.
Schmid, W. (1975), The Micronucleus Test, Mutation Res., 31, str. 9–15.
Heddle, J.A., Salamone, M.F., Hite, M., Kirkhart, B., Mavournin, K., MacGregor, J.G. and Newell, G.W.
Heddle, J. A., Salamone, M. F., Hite, M., Kirkhart, B., Mavournin, K., MacGregor, J. G., in Newell, G. W.
Mavournin, K.H., Blakey, D.H., Cimino, M.C., Salamone, M.F. and Heddle, J.A., (1990) The In Vivo Micronucleus Assay in Mammalian Bone Marrow and Peripheral Blood.
Mavournin, K. H., Blakey, D. H., Cimino, M. C, Salamone, M. F., in Heddle, J. A. (1990), The In Vivo Micronucleus Assay in Mammalian Bone Marrow and Peripheral Blood.
Environmental Protection Agency Gene-Tox Program, Mutation Res., 239, p. 29-80.
Environmental Protection Agency Gene-Tox Program, Mutation Res., 239, str. 29–80.
Iin: ‘Developments in Science and Practice of Toxicology’, Ed.
N., in Wehr, C. M. (1983), Micronuclei in Circulating Erythrocytes: A Rapid Screen for Chromosomal Damage During Routine Toxicity Testing in Mice, v: Developments in Science and Practice of Toxicology, izd.
Miya, Elsevier, Amsterdam, p. 555-558.
Elsevier, Amsterdam, str. 555–558.