natgillin/translations-raw huggingface dataset:
Měly by být uvedeny údaje o toxicitě a klinických známkách podle odstavce 34.
Important factors for consideration should include the route of administration (based on likely human exposure route(s)), the predicted tissue distribution, and the possible mechanism of action.
Použité statistické testy by měly brát v úvahu zvíře jako experimentální jednotku.
Tissues (or tissue homogenates) should be stored at or below – 70 °C and be used for DNA isolation within 5 years.
Zkoušená chemická látka, pro kterou výsledky nesplňují výše uvedená kritéria v žádné tkáni, je v této zkoušce považována za nemutagenní.
Isolated DNA, stored refrigerated at 4 °C in appropriate buffer, should be used optimally for mutation analysis within 1 year.
Při hodnocení biologického významu reakce může být vodítkem posouzení, zda jsou zjištěné hodnoty uvnitř nebo vně rozsahu historických kontrolních hodnot (32).
the route of administration or site of first contact (e.g. glandular stomach if administration is oral, lung if administration is through inhalation, or skin if topical application has been used);
identifikační údaje a číslo CAS, je-li známo,
and 2) pharmacokinetic parameters observed in general toxicity studies, which indicate tissue disposition, retention or accumulation, or target organs for toxicity.
zdroj, číslo šarže, je-li k dispozici,
If studies are conducted to follow up carcinogenicity studies, target tissues for carcinogenicity should be considered.
skupenství a čistota,
The choice of tissues for analysis should maximise the detection of chemicals that are direct-acting in vitro mutagens, rapidly metabolised, highly reactive or poorly absorbed, or those for which the target tissue is determined by route of administration (6).
fyzikálně-chemické vlastnosti významné pro provedení studie,
In the absence of background information and taking into consideration the site of contact due to route of administration, the liver and at least one rapidly dividing tissue (e.g. glandular stomach, bone marrow) should be evaluated for mutagenicity.
stabilita zkoušené chemické látky, je-li známa.
In most cases, the above requirements can be achieved from analyses of two carefully selected tissues, but in some cases, three or more would be needed.
Rozpouštědlo/vehikulum:
If there are reasons to be specifically concerned about germ cell effects, including positive responses in somatic cells, germ cell tissues should be evaluated for mutations.
zdůvodnění volby vehikula,
Methods of Measurement
rozpustnost a stabilita zkoušené chemické látky v rozpouštědle/vehikulu, je-li známa,
Standard laboratory or published methods for the detection of mutants are available for the recommended transgenic models:
příprava potravy, pitné vody nebo inhalačních aplikačních forem,
lacZ lambda bacteriophage and plasmid (30);
analytická stanovení aplikační formy (např. stabilita, homogenita, nominální koncentrace).
lacI mouse (2) (18);
použitý druh/kmen a odůvodnění výběru,
gpt delta mouse (22);
počet, stáří a pohlaví zvířat,
gpt delta rat (28);
zdroj, podmínky chovu, potrava atd.,
Modifications should be justified and properly documented.
individuální hmotnost zvířat na počátku zkoušky, včetně rozpětí tělesné hmotnosti, střední hodnoty a směrodatné odchylky pro každou skupinu.
Data from multiple packagings can be aggregated and used to reach an adequate number of plaques or colonies.
údaje o pozitivní a negativní (vehikulum/rozpouštědlo) kontrole,
However, the need for a large number of packaging reactions to reach the appropriate number of plaques may be an indication of poor DNA quality.
údaje ze studie pro stanovení rozmezí dávek,
In such cases, data should be considered cautiously because they may be unreliable.
podrobnosti o přípravě zkoušené chemické látky,
The optimal total number of plaques or colonies per DNA sample is governed by the statistical probability of detecting sufficient numbers of mutants at a given spontaneous mutant frequency.
zdůvodnění způsobu podávání,
In general, a minimum of 125000 to 300000 plaques is required if the spontaneous mutant frequency is in the order of 3 × 10–5 (15).
metody zjišťování toxicity, včetně případně histopatologických nebo hematologických analýz a četnosti, s jakou jsou prováděna pozorování zvířat, a četnosti vážení,
For the Big Blue® lacI assay, it is important to demonstrate that the whole range of mutant colour phenotypes can be detected by inclusion of appropriate colour controls concurrent with each plating.
metody ověřování, zda se zkoušená chemická látka dostala k cílové tkáni, nebo ověřování obecné cirkulace, pokud byly získány negativní výsledky,
Tissues and the resulting samples (items) should be processed and analysed using a block design, where items from the vehicle/solvent control group, the positive control group (if used) or positive control DNA (where appropriate), and each treatment group are processed together.
skutečná dávka (mg/kg tělesné hmotnosti na den) vypočítaná z koncentrace zkoušené chemické látky v potravě/pitné vodě (ppm) a ze spotřeby, je-li to relevantní,
Treatment of Results
podrobnosti o jakosti krmení a vody,
Individual animal data should be presented in tabular form.
podrobný popis harmonogramů aplikace a odběru vzorků a odůvodnění výběru konkrétního schématu,
The experimental unit is the animal.
způsob utracení,
The report should include the total number of plaque-forming units (pfu) or colony-forming units (cfu), the number of mutants, and the mutant frequency for each tissue from each animal.
postupy izolace a uchovávání tkání,
If there are multiple packaging/rescue reactions, the number of reactions per DNA sample should be reported.
metody izolace genomické DNA hlodavců, získání transgenu z genomické DNA a přenos transgenní DNA do bakteriálního hostitele,
While data for each individual reaction should be retained, only the total pfu or cfu need be reported.
zdroje a čísla šarží všech buněk, sad a chemických činidel (je-li to relevantní),
Data on toxicity and clinical signs as per paragraph 34 should be reported.
metody počítání mutací,
Any sequencing results should be presented for each mutant analysed, and resulting mutation frequency calculations for each animal and tissue should be shown.
metody molekulární analýzy mutací a použití při korekci pro klonalitu a/nebo výpočet četností mutací, jsou-li použitelné.
Statistical Evaluation and Interpretation of Results
Výsledky:
There are several criteria for determining a positive result, such as a dose-related increase in the mutant frequency, or a clear increase in the mutant frequency in a single dose group compared to the solvent/vehicle control group.
stav zvířat před zkouškou a během zkoušky, včetně známek toxicity,
At least three treated dose groups should be analysed in order to provide sufficient data for dose-response analysis.
tělesná hmotnost a hmotnost orgánů při utracení,
While biological relevance of the results should be the primary consideration, appropriate statistical methods may be used as an aid in evaluating the test results (4) (14) (15) (25) (26).
pro každou tkáň/zvíře počet mutací, počet hodnocených plaků nebo kolonií, četnost mutací,
Statistical tests used should consider the animal as the experimental unit.
pro každou tkáň/skupinu zvířat počet reakcí sbalování na jeden vzorek DNA, celkový počet mutací, střední četnost mutací, směrodatná odchylka,
A test chemical for which the results do not meet the above criteria in any tissue is considered non-mutagenic in this assay.
podle možnosti závislost odpovědi na dávce,
For biological relevance of a negative result, tissue exposure should be confirmed.
pro každou tkáň/zvíře počet nezávislých mutací a střední četnost mutací, pokud byla provedena molekulární analýza mutací,
For DNA sequencing analyses, a number of statistical approaches are available to assist in interpreting the results (1) (5) (9) (19).
souběžné a dosavadní údaje o negativní kontrole s rozpětími, středními hodnotami a směrodatnými odchylkami,
Consideration of whether the observed values are within or outside of the historical control range can provide guidance when evaluating the biological significance of the response (32).
údaje o souběžné pozitivní kontrole (nebo nesouběžné pozitivní kontrole DNA),
identification data and CAS no, if known;
analytická stanovení, jsou-li k dispozici (např. koncentrace DNA použité při sbalování, údaje o sekvenování DNA),
source, lot number if available;
použité statistické analýzy a metody.
physical nature and purity;
Závěr
physiochemical properties relevant to the conduct of the study;
Skopek (1987), ‚Statistical Test for the Comparison of Samples from Mutational Spectra‘, J.
stability of the test chemical, if known;
Mol.
Solvent/vehicle:
, ‚A more Efficient Big Blue® Protocol Improves Transgene Rescue and Accuracy in an Adduct and Mutation Measurement‘, Mutation Res., 518:
justification for choice of vehicle;
Gossen and J.
solubility and stability of the test chemical in the solvent/vehicle, if known;
Vijg (1995), ‚Plasmid-based Transgenic Mouse Model for Studying in vivo Mutations‘Nature, 377(6550):
preparation of dietary, drinking water or inhalation formulations;
Gorelick (1995), ‚Statistical Design and Analysis of Mutation Studies in Transgenic Mice‘, Environ.
analytical determinations on formulations (e.g. stability, homogeneity, nominal concentrations);
Gorelick (1996), ‚Mutational Spectra in Transgenic Animal Research: Data Analysis and Study Design Based upon the Mutant or Mutation Frequency‘, Environ.
species/strain used and justification for the choice;
Brooks, B.
number, age and sex of animals;
Burlinson, J.
source, housing conditions, diet, etc.;
Mirsalis, B.
individual weight of the animals at the start of the test, including body weight range, mean and standard deviation for each group;
Myhr, L.
positive and negative (vehicle/solvent) control data;
Recio and V.
data from the range-finding study;
Thybaud (1999), ‚Transgenic Mouse Mutation Assay Systems can Play an important Role in Regulatory Mutagenicity Testing in vivo for the Detection of Site-of-contact Mutagens‘, Mutagenesis, 14(1):
details of test chemical preparation;
Soper(1995), ‚Temporal and Molecular Characteristics of Mutations Induced by Ethylnitrosourea in Germ Cells Isolated from Seminiferous Tubules and in Spermatozoa of lacZ Transgenic Mice‘, Proc.
rationale for route of administration;
Soper and J.
methods for measurement of animal toxicity, including, where available, histopathological or haematological analyses and the frequency with which animal observations and body weights were taken;
Jiao (1997), ‚Toward an Understanding of the Use of Transgenic Mice for the Detection of Gene Mutations in Germ Cells‘, Mutation Res., 388(2-3):
methods for verifying that the test chemical reached the target tissue, or general circulation, if negative results are obtained;
Tindall (2000), ‚Bayesian Analysis of Mutational Spectra‘, Genetics, 156:
actual dose (mg/kg body weight/day) calculated from diet/drinking water test chemical concentration (ppm) and consumption, if applicable;
Knook and J.
details of food and water quality;
Vijg(1989), ‚Efficient Rescue of Integrated Shuttle Vectors from Transgenic Mice: a Model for Studying Mutations in vivo‘, Proc.
detailed description of treatment and sampling schedules and justifications for the choices;
Gossen, J.A. and J.
method of euthanasia;
Vijg (1993), ‚A Selective System for lacZ-Phage using a Galactose-sensitive E. coli Host‘, Biotechniques, 14(3):
procedures for isolating and preserving tissues;
, ‚Somatic Gene Mutation and Human Disease other than Cancer‘, Mutation Res., 543:
methods for isolation of rodent genomic DNA, rescuing the transgene from genomic DNA, and transferring transgenic DNA to a bacterial host;
, ‚Somatic Gene Mutation and Human Disease other than Cancer: an Update‘, Mutation Res., 705:
source and lot numbers of all cells, kits and reagents (where applicable);
Douglas and D.
methods for enumeration of mutants;
Krewski (1998), ‚Statistical Analysis of lacZ Mutant Frequency Data from Muta™Mouse Mutagenicity Assays‘, Mutagenesis, 13(3):
methods for molecular analysis of mutants and use in correcting for clonality and/or calculating mutation frequencies, if applicable;
Skopek, V.
Results:
Thybaud, K.R.Tindall and N.
animal condition prior to and throughout the test period, including signs of toxicity;
Yajima (2000), ‚In vivo Transgenic Mutation Assays‘, Environ.
body and organ weights at sacrifice;
Douglas (2003), ‚Treatment and Sampling Protocols for Transgenic Mutation Assays‘, Environ.
for each tissue/animal, the number of mutants, number of plaques or colonies evaluated, mutant frequency;
Muller, B.
for each tissue/animal group, number of packaging reactions per DNA sample, total number of mutants, mean mutant frequency, standard deviation;
Paul, S.
dose-response relationship, where possible;
Adhya and S.
for each tissue/animal, the number of independent mutants and mean mutation frequency, where molecular analysis of mutations was performed;
Garges (1996), ‚Analysis of Genetic Instability during Mammary Tumor Progression using a novel Selection-based Assay for in vivo Mutations in a Bacteriophage λ Transgene Target‘, Proc.
concurrent and historical negative control data with ranges, means and standard deviations;
Burns (2008), ‚Comparison of Induced and Cancer-associated Mutational Spectra using Multivariate Data Analysis‘, Carcinogenesis, 29(4):
concurrent positive control (or non-concurrent DNA positive control) data;
Nohmi, T., M.
analytical determinations, if available (e.g. DNA concentrations used in packaging, DNA sequencing data);
Katoh, H.
statistical analyses and methods applied;
Matsui, M.
Skopek (1987), “Statistical Test for the Comparison of Samples from Mutational Spectra”, J. Mol.
Yamada, M.
, “A more Efficient Big Blue® Protocol Improves Transgene Rescue and Accuracy in an Adduct and Mutation Measurement”, Mutation Res., 518:
Watanabe, M.
Gossen and J. Vijg (1995), “Plasmid-based Transgenic Mouse Model for Studying in vivo Mutations”Nature, 377(6550):
Suzuki, N.
Gorelick (1995), “Statistical Design and Analysis of Mutation Studies in Transgenic Mice”, Environ.
Horiya, O.
Gorelick (1996), “Mutational Spectra in Transgenic Animal Research: Data Analysis and Study Design Based upon the Mutant or Mutation Frequency”, Environ.
Ueda, T.
Brooks, B. Burlinson, J. Mirsalis, B. Myhr, L. Recio and V. Thybaud (1999), “Transgenic Mouse Mutation Assay Systems can Play an important Role in Regulatory Mutagenicity Testing in vivo for the Detection of Site-of-contact Mutagens”, Mutagenesis, 14(1):
Shibuya, H.
Soper(1995), “Temporal and Molecular Characteristics of Mutations Induced by Ethylnitrosourea in Germ Cells Isolated from Seminiferous Tubules and in Spermatozoa of lacZ Transgenic Mice”, Proc.
Ikeda and T.
Soper and J. Jiao (1997), “Toward an Understanding of the Use of Transgenic Mice for the Detection of Gene Mutations in Germ Cells”, Mutation Res., 388(2-3):
Sofuni (1996), ‚A new Transgenic Mouse Mutagenesis Test System using Spi – and 6-thioguanine Selections‘, Environ.
Tindall (2000), “Bayesian Analysis of Mutational Spectra”, Genetics, 156:
Nohmi, T., M.
Knook and J. Vijg(1989), “Efficient Rescue of Integrated Shuttle Vectors from Transgenic Mice: a Model for Studying Mutations in vivo”, Proc.
Suzuki, K.
Gossen, J.A. and J. Vijg (1993), “A Selective System for lacZ-Phage using a Galactose-sensitive E. coli Host”, Biotechniques, 14(3):
Masumura, M.
, “Somatic Gene Mutation and Human Disease other than Cancer”, Mutation Res., 543:
Yamada, K.
, “Somatic Gene Mutation and Human Disease other than Cancer: an Update”, Mutation Res., 705:
Matsui, O.
Douglas and D. Krewski (1998), “Statistical Analysis of lacZ Mutant Frequency Data from Muta™Mouse Mutagenicity Assays”, Mutagenesis, 13(3):
Ueda, H.
Skopek, V. Thybaud, K.R.Tindall and N. Yajima (2000), “In vivo Transgenic Mutation Assays”, Environ.
Suzuki, M.
Douglas (2003), “Treatment and Sampling Protocols for Transgenic Mutation Assays”, Environ.
Katoh, H.
Muller, B. Paul, S. Adhya and S. Garges (1996), “Analysis of Genetic Instability during Mammary Tumor Progression using a novel Selection-based Assay for in vivo Mutations in a Bacteriophage λ Transgene Target”, Proc.
Ikeda and T.
Short (1990), “The Use of Transgenic Mice for Short-term, in vivo Mutagenicity Testing”, Genet.
Sofuni (1999), ‚Spi – Selection: an Efficient Method to Detect γ-ray-induced Deletions in Transgenic Mice‘, Environ.
Burns (2008), “Comparison of Induced and Cancer-associated Mutational Spectra using Multivariate Data Analysis”, Carcinogenesis, 29(4):
Masumura (2000), ‚Recent Advances in the Protocols of Transgenic Mouse Mutation Assays‘, Mutation Res., 455(1–2):
Nohmi, T., M. Katoh, H. Suzuki, M. Matsui, M. Yamada, M. Watanabe, M. Suzuki, N. Horiya, O. Ueda, T. Shibuya, H. Ikeda and T. Sofuni (1996), “A new Transgenic Mouse Mutagenesis Test System using Spi– and 6-thioguanine Selections”, Environ.
Tindall (1995), ‚Study Design and Sample Sizes for a lacI Transgenic Mouse Mutation Assay‘, Environ.
OECD (2000), Guidance Document on the Recognition, Assessment and Use of Clinical Signs as Humane Endpoints for Experimental Animals Used in Safety Evaluation, Series on Testing and Assessment, No 19, ENV/JM/MONO(2000)7, OECD, Paris.
Yauk (2006), ‚Detection of Induced Male Germline Mutation: Correlations and Comparisons between Traditional Germline Mutation Assays, Transgenic Rodent Assays and Expanded Simple Tandem Repeat Instability Assays‘, Mutation.
Tindall (1995), “Study Design and Sample Sizes for a lacI Transgenic Mouse Mutation Assay”, Environ.
Yamada, H.
Kurata, M. Takamune, M. Yamada, H. Sanada, T. Umemura, A. Nishikawa and T. Nohmi (2010), “Integration of in vivo Genotoxicity and Short-term Carcinogenicity Assays using F344 gpt delta Transgenic Rats: in vivo Mutagenicity of 2,4-diaminotoluene and 2,6-diaminotoluene Structural Isomers”, Toxicol.
Sanada, T.
Martus, J.C. Mirsalis, T. Suzuki and N. Yajima (2003), “In vivo Transgenic Mutation Assays”, Mutation Res., 540:
Umemura, A.
Douglas (1996), “Bacteriophage λ and Plasmid lacZ Transgenic Mice for studying Mutations in vivo” in:
Nishikawa and T.
Douglas (2005), “A lacZ Transgenic Mouse Assay for the Detection of Mutations in Follicular Granulosa Cells”, Mutation Res., 578(1-2):
Nohmi (2010), ‚Integration of in vivo Genotoxicity and Short-term Carcinogenicity Assays using F344 gpt delta Transgenic Rats: in vivo Mutagenicity of 2,4-diaminotoluene and 2,6-diaminotoluene Structural Isomers‘, Toxicol.
Martus, V. Thybaud (2011), “Compilation and Use of Genetic Toxicity Historical Control Data”, Mutation Res., doi:10.1016/j.mrgentox.2010.09.007.
Martus, J.C. Mirsalis, T.
OECD (2011), Retrospective Performance Assessment of OECD Test Guideline on Transgenic Rodent Somatic and Germ Cell Gene Mutation Assays, Series on Testing and Assessment, No 145, ENV/JM/MONO(2011)20, OECD, Paris.
Suzuki and N.
, “Kinetics of spermatogenesis in mammals seminiferous epithelium cycle and spermatogonial renewal”.
Yajima (2003), ‚In vivo Transgenic Mutation Assays‘, Mutation Res., 540:
, “The Epididymis”, in Neil, J.D., Pfaff, D.W., Chalis, J.R.G., de Kretser, D.M., Richards, J.S., and P. M, Wassarman (eds.), Physiology of Reproduction, Elsevier, the Netherlands, pp. 1071-1148.
Douglas (1996), ‚Bacteriophage λ and Plasmid lacZ Transgenic Mice for studying Mutations in vivo‘ in:
, “Effects of male germ-cell stage on the frequency, nature, and spectrum of induced specific-locus mutations in the mouse”, Genetica, 122:
Douglas (2005), ‚A lacZ Transgenic Mouse Assay for the Detection of Mutations in Follicular Granulosa Cells‘, Mutation Res., 578(1–2):
Administration period
Martus, V.
the total period during which an animal is dosed.
Thybaud (2011), ‚Compilation and Use of Genetic Toxicity Historical Control Data‘, Mutation Res., doi:10.1016/j.mrgentox.2010.09.007.
Base pair substitution
OECD (2011), Retrospective Performance Assessment of OECD Test Guideline on Transgenic Rodent Somatic and Germ Cell Gene Mutation Assays, Series on Testing and Assessment, No 145, ENV/JM/MONO(2011)20, OECD, Paris.
a type of mutation that causes the replacement of a single DNA nucleotide base with another DNA nucleotide base.
, ‚Kinetics of spermatogenesis in mammals seminiferous epithelium cycle and spermatogonial renewal‘.
Capsid
, ‚The Epididymis‘, in Neil, J.D., Pfaff, D.W., Chalis, J.R.G., de Kretser, D.M., Richards, J.S., and P.
the protein shell that surrounds a virus particle.
M, Wassarman (eds.), Physiology of Reproduction, Elsevier, the Netherlands, s. 1071–1148.
a substance or a mixture.
, ‚Effects of male germ-cell stage on the frequency, nature, and spectrum of induced specific-locus mutations in the mouse‘, Genetica, 122:
Clonal expansion
DEFINICE
the production of many cells from a single (mutant) cell.
Bodová mutace
Colony-forming unit (cfu)
Delece
a measure of viable bacterial numbers.
Doba odběru vzorků
Concatamer
Doba podávání
a long continuous biomolecule composed of multiple identical copies linked in series.
celková doba, během níž jsou zvířeti podávány dávky.
Cos site
Elektroporace
a 12-nucleotide segment of single-stranded DNA that exists at both ends of the bacteriophage lambda's double-stranded genome.
aplikace elektrických impulzů pro zvýšení propustnosti buněčných membrán.
Deletion
Extrabinomické rozdělení větší variabilita při opakovaných odhadech podílu populace, než by se čekalo, pokud by populace měla binomické rozdělení.
the application of electric pulses to increase the permeability of cell membranes.
Chemická látka
Endogenous gene
látka nebo směs.
a gene native to the genome.
Inserce doplnění jednoho nebo více párů bází do sekvence DNA.
Extrabinomial variation
Jednotka tvořící kolonii (cfu)
a genetic mutation caused by insertions or deletions of a number of nucleotides that is not evenly divisible by three within a DNA sequence that codes for a protein/peptide.
bílkovinné pouzdro, které obklopuje virovou částici.
Large deletions
Konkatemer dlouhá spojitá biomolekula složená z mnoha identických kopií spojených do série.
the covalent linking of two ends of DNA molecules using DNA ligase.
Ligace
Mitogen
kovalentní vazba dvou konců molekul DNA pomocí ligázy DNA.
a chemical that stimulates a cell to commence cell division, triggering mitosis (i.e. cell division).
Místo cos
Neutral gene
ý segment jednořetězcové DNA, který se vyskytuje na obou koncích dvouřetězcového genomu bakteriofágu lambda.
a gene that is not affected by positive or negative selective pressures.
Neutrální gen
Commonly used to package DNA cloned onto a lambda vector (separated by cos sites) into infectious lambda particles.
gen, který není dotčen tlaky pozitivní nebo negativní selekce.
Packaging efficiency
Posunová mutace
the efficiency with which packaged bacteriophages are recovered in host bacteria.
Pozitivní selekce metoda, díky níž přežívají pouze mutace.
Plaque forming unit (pfu)
Reporterový gen
a measure of viable bacteriophage numbers.
gen, jehož mutace se snadno zjišťuje.
Point mutation
Sbalování (packaging)
a general term for a mutation affecting only a small sequence of DNA including small insertions, deletions, and base pair substitutions.
syntéza infekčních částic fágu z přípravy bílkovin kapsidy a konce fágu a konkatemeru molekul DNA fágu.
Positive selection
Shuttle vektor
a method that permits only mutants to survive.
Substituce páru bází
Reporter gene
Transgenní
a gene whose mutant gene product is easily detected.
patřící organismu, týkající se organismu nebo organismus, jehož genom byl změněn transferem genu nebo genů z jiných druhů.
Sampling time
Účinnost sbalování
the end of the period of time, prior to sacrifice, during which the chemical is not administered and during which unprocessed DNA lesions are fixed into stable mutations.
účinnost, se kterou jsou sbalené bakteriofágy znovu zachycovány v hostitelských bakteriích.
Shuttle vector
Velké delece
a vector constructed so that it can propagate in two different host species;