natgillin/translations-raw huggingface dataset:
Gross necropsy and organ weight results should be assessed in context with observations made in other repeat-dose studies, when feasible.
Cooper (2007), ‚The Rodent Estrous Cycle: Characterization of Vaginal Cytology and its Utility in Toxicological Studies‘, Birth Defects Research, Part B, 80 (2), 84 - 97.
Decreases in offspring growth might be considered in relationship to an influence of the test chemical on milk composition (29).
, ‚Cycles and Seasons‘, in C.R.
Cohort 2 (Developmental neurotoxicity)
Reynolds (1999), ‚Interpreting the Toxicologic Significance of Alterations in Anogenital Distance: Potential for Confounding Effects of Progeny Body Weights‘, Reproductive Toxicology, 13:
Neurobehavioral and neuropathology results should be interpreted in the context of all findings, using a weight-of-evidence approach with expert judgment.
Weiner (1977), ‚Preputial Separation as an External Sign of Pubertal Development in the Male Rat‘, Biological Reproduction, 17, 298 - 303.
The evaluation of developmental neurotoxicity, including human epidemiological studies or case reports, and experimental animal studies (e.g. toxicokinetic data, structure-activity information, data from other toxicity studies) should be included in this characterisation.
, ‚Use of SRBC Antibody Responses for Immunotoxicity Testing‘, Methods, 41, 9 -19.
For guidance on the interpretation of developmental neurotoxicity results, refer to test method B.53 (35) and Tyl et al., 2008 (31).
Herzyk (2004), ‚Primary Antibody Response to Keyhole Limpet Hemocyanin in Rat as a Model for Immunotoxicity Evaluation‘, Toxicology, 197, 23 - 35.
Cohort 3 (Developmental immunotoxicity)
Gray, L.E., J. Ostby, J. Ferrell, G. Rehnberg, R. Linder, R. Cooper, J. Goldman, V. Slott and J. Laskey (1989), ‚A Dose-Response Analysis of Methoxychlor-Induced Alterations of Reproductive Development and Function in the Rat‘, Fundamental and Applied Toxicology, 12, 92 -108.
Significance of the outcome of TDAR may be supported by other effects on immunologically-related indicators (e.g. bone marrow cellularity, weight and histopathology of lymphoid tissues, lymphocyte subset distribution).
Suarez (1991), ‚The Method of Sperm Collection Significantly Influences Sperm Motion Parameters Following Ethane Dimethanesulfonate Administration in the Rat‘.
Effects established by TDAR may be less meaningful in case of other toxicities observed at lower exposure concentrations.
Reproductive Toxicology,5, 39 - 44.
OECD Guidance Document 43 should be consulted for aid in the interpretation of reproduction and neurotoxicity results (26).
Wise (1996), ‚Methods for Assessing Sperm Motility, Morphology, and Counts in the Rat, Rabbit, and Dog: a Consensus Report‘, Reproductive Toxicology, 10, 237 - 244.
Whitby (2006), “A Tiered Approach to Life Stages Testing for Agricultural Chemical Safety Assessment”, Critical Reviews in Toxicology, 36, 69-98.
Russell and S. Schrader (1992), ‚Methods for Assessing Rat Sperm Motility‘, Reproductive Toxicology, 6, 267 - 273.
Forsythe (1999), “Phytoestrogen Content of Purified Open and Closed Formula Laboratory Animal Diets”, Lab.
Suarez (1992), ‚Direct Effects of Ethane Dimethanesulphonate on Epididymal Function in Adult Rats: an In Vitro Demonstration‘, Journal of Andrology, 13, 409 - 421.
Sci., 49, 530- 536.
Perreault (1991), ‚Rat Sperm Motility Analysis: Methodologic Considerations‘, Reproductive Toxicology, 5, 449 - 458.
Moser, V.C., I. Walls and T. Zoetis (2005), “Direct Dosing of Preweaning Rodents in Toxicity Testing and Research: Deliberations of an ILSI RSI Expert Working Group”, International Journal of Toxicology, 24, 87-94.
Perreault (1993), ‚Computer-Assisted Sperm Analysis of Rodent Epididymal Sperm Motility Using the Hamilton-Thorn Motility Analyzer‘, Methods in Toxicology, Part A, Academic, Orlando, Florida. s. 319 - 333.
Goodman (1999), “Stimulating Research to Improve the Scientific Basis of Risk Assessment”, Toxicological Sciences, 49, 1-4.
Smith (1989), ‚The Automated Analysis of Rat Sperm Motility Following Subchronic Epichlorhydrin Administration: Methodologic and Statistical Considerations‘, Journal of Andrology, 10, 401 - 415.
Palmer (1995), “Detection of Effects on Male Reproduction — a Literature Survey”, Journal of the American College of Toxicologists, 14, 293-327.
Suarez (1992), ‚Endpoints of Spermatoxicity in the Rat After Short Duration Exposures to Fourteen Reproductive Toxicants‘, Reproductive Toxicology, 6, 491 - 505.
Mangelsdorf, I., J. Buschmann and B. Orthen (2003), “Some Aspects Relating to the Evaluation of the Effects of Chemicals on Male Fertility”, Regulatory Toxicology and Pharmacology, 37, 356-369.
OECD (2008), Guidance Document on Mammalian Reproductive Toxicity Testing and Assessment, Series on Testing and Assessment, No.
“Collaborative work to evaluate toxicity on male reproductive organs by repeated dose studies in rats — overview of the studies”, Journal of Toxicological Sciences, 25, 1-21.
43, ENV/JM/MONO(2008)16, OECD, Paríž.
, “Evaluation of Testicular Toxicology: A Synopsis and Discussion of the Recommendations Proposed by the Society of Toxicologic Pathology”, Birth Defects Research, Part B, 68, 408-415.
Working, P.K., M. Hurtt (1987), ‚Computerized Videomicrographic Analysis of Rat Sperm Motility‘, Journal of Andrology, 8, 330 - 337.
Cooper (2007), “The Rodent Estrous Cycle: Characterization of Vaginal Cytology and its Utility in Toxicological Studies”, Birth Defects Research, Part B, 80 (2), 84-97.
Bolin, B., R. Garman, K. Jensen, G. Krinke, B. Stuart, and an ad Hoc Working Group of the STP Scientific and Regulatory Policy Committee (2006), ‚A »Best Practices« Approach to Neuropathologic Assessment in Developmental Neurotoxicity Testing – for Today‘, Toxicological Pathology, 34, 296 - 313.
, “Cycles and Seasons”, in C.R.
Stütz, N., B. Bongiovanni, M. Rassetto, A. Ferri, A.M. Evangelista de Duffard, and R. Duffard (2006), ‚Detection of 2,4-dichlorophenoxyacetic Acid in Rat Milk of Dams Exposed During Lactation and Milk Analysis of their Major Components‘, Food Chemicals Toxicology, 44, 8 - 16.
I. Germ Cells and Fertilization, Cambridge, New York.
Forsythe (2007), ‚Variations in Phytoestrogen Content between Different Mill Dates of the Same Diet Produces Significant Differences in the Time of Vaginal Opening in CD-1 Mice and F344 Rats but not in CD Sprague Dawley Rats‘, Environmental health perspectives, 115(12), 1717 - 1726.
Reynolds (1999), “Interpreting the Toxicologic Significance of Alterations in Anogenital Distance: Potential for Confounding Effects of Progeny Body Weights”, Reproductive Toxicology, 13:
Sheets and T.J. Sobotka (2008), ‚Identification and Interpretation of Developmental Neurotoxicity Effects: a Report from the ILSI Research Foundation/Risk Science Institute Expert Working Group on Neurodevelopmental Endpoints‘, Neurotoxicology and Teratology, 30:
Weiner (1977), “Preputial Separation as an External Sign of Pubertal Development in the Male Rat”, Biological Reproduction, 17, 298-303.
OECD (1996), Combined Repeated Dose Toxicity Study with the Reproduction/Developmental Toxicity Screening Test, OECD Guideline for Testing of Chemicals, No.
, “Use of SRBC Antibody Responses for Immunotoxicity Testing”, Methods, 41, 9-19.
422, OECD, Paríž.
Herzyk (2004), “Primary Antibody Response to Keyhole Limpet Hemocyanin in Rat as a Model for Immunotoxicity Evaluation”, Toxicology, 197, 23-35.
Kapitola B.43 tejto prílohy, Štúdia neurotoxicity u hlodavcov
Gray, L.E., J. Ostby, J. Ferrell, G. Rehnberg, R. Linder, R. Cooper, J. Goldman, V. Slott and J. Laskey (1989), “A Dose-Response Analysis of Methoxychlor-Induced Alterations of Reproductive Development and Function in the Rat”, Fundamental and Applied Toxicology, 12, 92-108.
OECD (2000), Guidance Document on the recognition, assessment, and use of clinical signs as humane endpoints for experimental animals used in safety evaluations, Series on Testing and Assessment, No.
Killian (1978), “Daily Sperm Production and Epididymal Sperm Reserves of Pubertal and Adult Rats”, Journal of Reproduction and Fertility,54, 103-107.
19, ENV/JM/MONO(2000)7, OECD, Paríž.
Suarez (1991), “The Method of Sperm Collection Significantly Influences Sperm Motion Parameters Following Ethane Dimethanesulfonate Administration in the Rat”.
Kapitola B.53 tejto prílohy, Štúdia vývojovej neurotoxicity
Reproductive Toxicology, 5, 39-44.
Kapitola B.54 tejto prílohy, Uterotrofický biologický test u hlodavcov:
Wise (1996), “Methods for Assessing Sperm Motility, Morphology, and Counts in the Rat, Rabbit, and Dog: a Consensus Report”, Reproductive Toxicology, 10, 237- 244.
Krátkodobý skríningový test na estrogénne vlastnosti
Russell and S. Schrader (1992), “Methods for Assessing Rat Sperm Motility”, Reproductive Toxicology, 6, 267-273.
Kapitola B.55 tejto prílohy, Hershbergerov biologický test u potkanov:
Suarez (1992), “Direct Effects of Ethane Dimethanesulphonate on Epididymal Function in Adult Rats: an In Vitro Demonstration”, Journal of Andrology, 13, 409-421.
Krátkodobý skríningový test na (anti)androgénne vlastnosti
Perreault (1991), “Rat Sperm Motility Analysis: Methodologic Considerations”, Reproductive Toxicology, 5, 449-458.
OECD (2009), Guidance Document for Histologic Evalution of Endocrine and Reproductive Test in Rodents, Series on Testing and Assessment, No.
Perreault (1993), “Computer-Assisted Sperm Analysis of Rodent Epididymal Sperm Motility Using the Hamilton-Thorn Motility Analyzer”, Methods in Toxicology, Part A, Academic, Orlando, Florida. pp. 319-333.
106, OECD, Paríž.
Smith (1989), "The Automated Analysis of Rat Sperm Motility Following Subchronic Epichlorhydrin Administration: Methodologic and Statistical Considerations", Journal of Andrology, 10, 401-415.
OECD (2011), Guidance Document on the Current Implementation of Internal Triggers in the Extended One Generation Reproductive Toxicity Study in the United States and Canada, Series on Testing and Assessment, No.
Suarez (1992), “Endpoints of Spermatoxicity in the Rat After Short Duration Exposures to Fourteen Reproductive Toxicants”, Reproductive Toxicology, 6, 491-505.
117, ENV/JM/MONO(2011)21, OECD, Paríž.
OECD (2008), Guidance Document on Mammalian Reproductive Toxicity Testing and Assessment, Series on Testing and Assessment, No 43, ENV/JM/MONO(2008)16, OECD, Paris.
151, OECD, Paríž.
Working, P.K., M. Hurtt (1987), “Computerized Videomicrographic Analysis of Rat Sperm Motility”, Journal of Andrology, 8, 330-337.
Kritériá a pozorovania zahrnuté vo funkčnej pozorovacej batérii (kohorta 2a)
Bolin, B., R. Garman, K. Jensen, G. Krinke, B. Stuart, and an ad Hoc Working Group of the STP Scientific and Regulatory Policy Committee (2006), “A “Best Practices” Approach to Neuropathologic Assessment in Developmental Neurotoxicity Testing — for Today”, Toxicological Pathology, 34, 296-313.
Domovská klietka a otvorený priestor
Stütz, N., B. Bongiovanni, M. Rassetto, A. Ferri, A.M. Evangelista de Duffard, and R. Duffard (2006), “Detection of 2,4-dichlorophenoxyacetic Acid in Rat Milk of Dams Exposed During Lactation and Milk Analysis of their Major Components”, Food Chemicals Toxicology, 44, 8-16.
Manipulácia
Forsythe (2007), “Variations in Phytoestrogen Content between Different Mill Dates of the Same Diet Produces Significant Differences in the Time of Vaginal Opening in CD-1 Mice and F344 Rats but not in CD Sprague Dawley Rats”, Environmental health perspectives, 115(12), 1717-1726.
Fyziológia
Sobotka (2008), “Identification and Interpretation of Developmental Neurotoxicity Effects: a Report from the ILSI Research Foundation/Risk Science Institute Expert Working Group on Neurodevelopmental Endpoints”, Neurotoxicology and Teratology, 30:
Postoj
OECD (1996), Combined Repeated Dose Toxicity Study with the Reproduction/Developmental Toxicity Screening Test, OECD Guideline for Testing of Chemicals, No 422, OECD, Paris.
Jednoduchosť odstránenia
Chapter B.43 of this Annex, Neurotoxicity Study in Rodents
Teplota
OECD (2000), Guidance Document on the recognition, assessment, and use of clinical signs as humane endpoints for experimental animals used in safety evaluations, Series on Testing and Assessment, No 19, ENV/JM/MONO(2000)7, OECD, Paris.
Nedobrovoľné šklbavé pohyby a svalové napätie
Chapter B.53 of this Annex, Developmental Neurotoxicity Study
Jednoduchosť zaobchádzania
Chapter B.54 of this Annex, Uterotrophic Bioassay in Rodents:
Palpebrálne zatvorenie
A short-term Screening Test for Oestrogenic Properties
Svalový tonus
Chapter B.55 of this Annex, Hershberger Bioassay in Rats:
Reakcia zreničky
A Short-term Screening Assay for (Anti)Androgenic Properties
Piloerekcia
OECD (2009), Guidance Document for Histologic Evaluation of Endocrine and Reproductive Test in Rodents, Series on Testing and Assessment, No 106, OECD, Paris.
Reakcia na priblíženie
OECD (2011), Guidance Document on the Current Implementation of Internal Triggers in the Extended One Generation Reproductive Toxicity Study in the United States and Canada, Series on Testing and Assessment, No 117, ENV/JM/MONO(2011)21, OECD, Paris.
Veľkosť zreničky
Extended One Generation Reproductive Toxicity Study, Series on Testing and Assessment, No 151, OECD, Paris.
Slinenie
Measures and observations included in the functional observational battery (Cohort 2A)
Reakcia na dotyk
Home Cage & Open Field
Slzenie
Manipulative
Sluchová reakcia
Physiologic
Vydávanie zvukov
Posture
Reakcia na stisnutie chvosta
Ease of removal
Odchov
Temperature
Polohová reakcia
Involuntary Clonic & Tonic
Odchýlky chôdze
Ease of handling
Slabosť dopadajúcich nôh
Palpebral Closure
Vzrušenie
Muscle Tone
Sila zovretia prednými končatinami
Pupil response
Sila zovretia zadnými končatinami
Approach Response
Škvrny
Pupil size
Respiračné odchýlky
Salivation
Chemikália
Touch Response
látka alebo zmes
Lacrimation
Testovaná chemikália
Auditory Response
akákoľvek látka alebo zmes testovaná pomocou tejto testovacej metódy.
Vocalisations
B.57.
Tail Pinch Response
SKÚŠKA STEROIDOGENÉZY H295R
Rearing
Táto testovacia metóda je rovnocenná s usmernením OECD na vykonávanie testov (TG) 456 (2011).
Righting Response
OECD spustila v roku 1998 prioritnú aktivitu na revidovanie a vypracovanie nových usmernení na vykonávanie testov na skríning a testovanie možných chemikálií narúšajúcich endokrinný systém.
Gait Abnormalities
Koncepčný rámec OECD na testovanie a hodnotenie chemikálií narúšajúcich endokrinný systém z roku 2002 pozostáva z piatich úrovní, pričom každá úroveň zodpovedá inej úrovni biologickej náročnosti (1).
Landing Foot Splay
Skúška in vitro steroidogenézy H295R (H295R) opísaná v tejto testovacej metóde používa ľudskú bunkovú líniu adrenokarcinómu (bunky NCI-H295R) a predstavuje ‚skúšku in vitro, ktorá poskytuje mechanistické údaje‘ na úrovni 2, ktoré sa používajú na účely skríningu a prioritizácie.
Arousal
Toto testovanie sa na vyšetrenie chemických účinkov na steroidogenézu, najmä na produkciu 17β-estradiolu (E2) a testosterónu (T), vypracovalo a štandardizovalo vo viacerých krokoch.
Forelimb Grip Strength
Skúška H295R sa optimalizovala a validovala (2) (3) (4) (5).
Stereotypy
Cieľom skúšky steroidogenézy H295R je určiť chemikálie, ktoré ovplyvňujú produkciu E2 a T. Skúškou H295R sa majú identifikovať xenobiotiká, ktorých cieľovým miestom/cieľovými miestami sú endogénne zložky, ktoré tvoria vnútrobunkovú biochemickú cestu začínajúcu sledom reakcií od cholesterolu po produkciu E2 a/alebo T. Skúškou H295R sa nemajú identifikovať chemikálie, ktoré ovplyvňujú steroidogenézu v dôsledku účinkov na os HPG (hypotalamus-hypofýza-pohlavné žľazy).
Hindlimb Grip Strength
Cieľom skúšky nie je poskytnúť odpoveď ÁNO/NIE, pokiaľ ide o potenciál chemikálie indukovať alebo obmedziť produkciu T a E2;
Bizarre Behaviour
v niektorých prípadoch však možno získať kvantitatívne výsledky (pozri odseky 53 a 54).
Stains
Výsledky skúšky sa vyjadrujú ako relatívne zmeny produkcie hormónov v porovnaní s kontrolami s aplikáciou rozpúšťadla.
Respiratory Abnormalities
Cieľom skúšky nie je poskytnúť konkrétne mechanistické informácie týkajúce sa interakcie testovanej chemikálie s endokrinným systémom.
Chemical
Vykonal sa výskum s použitím bunkovej línie na identifikáciu účinkov na špecifické enzýmy a prostredné hormóny, ako je napríklad progesterón (2).
A substance or a mixture.
Vymedzenia pojmov a skratky použité v tejto testovacej metóde sú opísané v dodatku.
Test Chemical
Podrobný protokol vrátane pokynov na prípravu roztokov, kultiváciu buniek a vykonávanie rôznych aspektov testu sú k dispozícii ako dodatok I až III k dokumentu OECD s názvom Multi-Laboratory Validation of the H295R Steroidogenesis Assay to Identify Modulators of Testosterone and Estradiol Production (4).
Any substance or mixture tested using this test method.
V biosyntéze pohlavných steroidných hormónov pôsobí päť rôznych enzýmov, ktoré katalyzujú šesť rôznych reakcií.
B.57 H295R STEROIDOGENESIS ASSAY
Enzymatická konverzia cholesterolu na pregnenolon enzýmom štiepiacim cholesterolový postranný reťazec (CYP11A) cytochrómu P450 (CYP) predstavuje prvý krok v sérii biochemických reakcií, ktoré kulminujú syntézou steroidných konečných produktov.
This test method is equivalent to OECD Test Guideline (TG) 456 (2011).
V závislosti od poradia ďalších dvoch reakcií sa steroidogenetická dráha rozdeľuje na dve dráhy, dráhu Δ5-hydroxysteroidu a dráhu Δ4-ketosteroidu, ktoré sa spájajú do produkcie androsténdiónu (obrázok č. 1).
The OECD initiated a high-priority activity in 1998 to revise existing, and to develop new, test guidelines for the screening and testing of potential endocrine disrupting chemicals.
Androsténdión sa mení na testosterón (T) dehydrogenáciou 17β-hydroxysteroidu (17β-HSD).
The 2002 OECD Conceptual Framework for Testing and Assessment of Endocrine Disrupting Chemicals comprises five levels, each level corresponding to a different level of biological complexity (1).
Testosterón je tak medziprodukt, ako aj konečný hormonálny produkt.
The in vitro H295R Steroidogenesis Assay (H295R) described in this test method utilises a human adreno-carcinoma cell line (NCI-H295R cells) and constitutes a level 2 “in vitro assay, providing mechanistic data”, to be used for screening and prioritisation purposes.
T sa u samcov môže meniť na dihydrotestosterón (DHT) 5α-reduktázou, ktorá sa nachádza v bunkových membránach, obale bunkového jadra a v endoplazmatickom retikule cieľových tkanív androgénnej činnosti, ako sú prostata a semenné mechúriky.
Development and standardisation of the assay as a screen for chemical effects on steroidogenesis, specifically the production of 17β-oestradiol (E2) and testosterone (T), was carried out in a multi–step process.
DHT je ako androgén podstatne silnejší ako T a považuje sa tiež za konečný hormón.
The H295R assay has been optimised and validated (2) (3) (4) (5).
Skúškou H295R sa nemeria DHP (pozri odsek 10).
The objective of the H295R Steroidogenesis Assay is to detect chemicals that affect production of E2 and T. The H295R assay is intended to identify xenobiotics that have as their target site(s) the endogenous components that comprise the intracellular biochemical pathway beginning with the sequence of reactions from cholesterol to the production of E2 and/or T. The H295R assay is not intended to identify chemicals that affect steroidogenesis due to effects on the hypothalamic-pituitary-gonadal (HPG) axis.
Enzým v steroidogénnej dráhe, ktorý premieňa androgénne chemikálie na estrogénne chemikálie, je aromatáza (CYP19).
The goal of the assay is to provide a YES/NO answer with regard to the potential of a chemical to induce or inhibit the production of T and E2;
CYP19 premieňa T na 17β-estradiol (E2) a androstendión na estrón.
however, quantitative results may be obtained in some cases (see paragraphs 53 and 54).
E2 a T sa považujú za konečné hormóny steroidogenézy.
The results of the assay are expressed as relative changes in hormone production compared with the solvent controls (SCs).
Špecifickosť činnosti lyázy CYP17 je u jednotlivých druhov pre prostredné substráty rozdielna.
The assay does not aim to provide specific mechanistic information concerning the interaction of the test chemical with the endocrine system.
U ľudí uprednostňuje tento enzým substráty dráhy Δ5-hydroxysteroidu (pregnenolon), zatiaľ čo u potkanov sa uprednostňujú substráty v dráhe Δ4-ketosteroidu (progesterón) (19).
Research has been conducted using the cell line to identify effects on specific enzymes and intermediate hormones such as progesterone (2).
Týmito rozdielmi činnosti lyázy CYP17 možno vysvetliť rozdielne reakcie jednotlivých druhov na chemikálie, ktoré menia steroidogenézu in vivo (6).
Definitions and abbreviations used in this test method are described in the Appendix.
Ukázalo sa, že bunky H295 najlepšie odrážajú model expresie enzýmu ľudskej dospelej nadobličky a produkcie steroidu (20), ale je známe, že exprimujú enzýmy pre dráhu Δ5-hydroxysteroidu a aj pre dráhu Δ4-ketosteroidu pre androgénnu syntézu (7) (11) (13) (15).
A detailed protocol including instructions on how to prepare solutions, cultivate cells and perform various aspects of the test is available as Appendix I-III to the OECD document “Multi-Laboratory Validation of the H295R Steroidogenesis Assay to Identify Modulators of Testosterone and Estradiol Production” (4).
Enzýmy sú označené kurzívou, hormóny sú označené tučným písmom a šípky označujú smer syntézy.
Enzymatic conversion of cholesterol to pregnenolone by the cytochrome P450 (CYP) cholesterol side-chain cleavage enzyme (CYP11A) constitutes the initial step in a series of biochemical reactions that culminate in synthesis of steroid end-products.
Dráhy/produkty pohlavných steroidov sú zakrúžkované.
Depending upon the order of the next two reactions, the steroidogenic pathway splits into two paths, the Δ5-hydroxysteroid pathway and Δ4-ketosteroid pathway, which converge in the production of androstenedione (Figure 1).
CYP = cytochróm P450;
Androstenedione is converted to testosterone (T) by 17β-hydroxysteroid dehydrogenase (17β-HSD).
HSD = hydroxysteroid-dehydrogenáza;
Testosterone is both an intermediate and end-hormone product.
DHEA = dehydroepiandrosterón.
In the male, T can be converted to dihydrotestosterone (DHT) by 5α-reductase, which is found in the cellular membranes, nuclear envelope, and endoplasmic reticulum of target tissues of androgenic action such as prostate and seminal vesicles.
Ľudská bunková línia adrenokarcinómu H295R je užitočný in vitro model skúmania účinkov na syntézu steroidných hormónov (2) (7) (8) (9) (10).
DHT is significantly more potent as an androgen than T and is also considered an end-product hormone.
Bunková línia H295R exprimuje gény, ktoré kódujú pre všetky kľúčové enzýmy pre steroidogenézu uvedenú skôr v texte (11) (15) (obrázok č. 1).
The H295R assay does not measure DHT (see paragraph 10).
Je to jedinečná vlastnosť, pretože expresia in vivo týchto génov je špecifická pre jednotlivé tkanivá a vývojové stupne, pričom zvyčajne žiadne tkanivo ani žiadny vývojový stupeň neexprimuje všetky gény zúčastňujúce sa na steroidogenéze (2).
The enzyme in the steroidogenic pathway which converts androgenic chemicals into oestrogenic chemicals is aromatase (CYP19).
Bunky H295R majú fyziologické charakteristiky buniek zonálne nediferencovaných ľudských fetálnych nadobličiek (11).
CYP19 converts T into 17β-oestradiol (E2) and androstenedione into oestrone.
Bunky predstavujú jedinečný systém in vitro, keďže majú schopnosť produkovať všetky steroidné hormóny, ktoré sa nachádzajú v kôre dospelej nadobličky a v pohlavných žľazách, čo umožňuje testovanie účinkov na syntézu kortikosteroidov a aj na produkciu pohlavných steroidných hormónov, ako sú androgény a estrogény, hoci skúška je validovaná len na zisťovanie T a E2.
E2 and T are considered end-product hormones of the steroidogenic pathway.
Zmeny zaznamenané systémom testovania vo forme zmeny produkcie T a E2 môžu byť výsledkom mnohých rôznych interakcií testovaných chemikálií so steroidogénnymi funkciami, ktoré exprimujú bunky H295R.
The specificity of the lyase activity of CYP17 differs for the intermediate substrates among species.
Medzi ne patrí zmena expresie, syntézy alebo funkcie enzýmov zúčastňujúcich sa na produkcii, premene alebo odstraňovaní steroidných hormónov (12) (13) (14).