Access the full text.
Sign up today, get DeepDyve free for 14 days.
J. Kamm, Kathleen Ashenfelter, C. Ehmann (1984)
Preclinical and Clinical Toxicology of Selected Retinoids
N. Brown (2002)
Selection of Test Chemicals for the ECVAM International Validation Study on In Vitro Embryotoxicity TestsAlternatives to Laboratory Animals, 30
S. Bremer, Andrew Worth, M. Paparella, K. Bigot, E. Kolossov, B. Fleischmann, J. Hescheler, M. Balls (2001)
Establishment of an in vitro reporter gene assay for developmental cardiac toxicity.Toxicology in vitro : an international journal published in association with BIBRA, 15 3
M. Seeley, E. Faustman (1998)
Evaluation of P19 cells for studying mechanisms of developmental toxicity: application to four direct-acting alkylating agents.Toxicology, 127 1-3
M. Paparella, E. Kolossov, B. Fleischmann, Juergen Hescheler, S. Bremer (2002)
The use of quantitative image analysis in the assessment of in vitro embryotoxicity endpoints based on a novel embryonic stem cell clone with endoderm-related GFP expression.Toxicology in vitro : an international journal published in association with BIBRA, 16 5
H. Spielmann (1997)
The embryonic stem cell test (EST), an in vitro embryotoxicity test using two permanent mouse cell lines : 3T3 fibroblasts and embryonic stem cells, 10
W. Wright, Mieczyslaw Piatyszek, W. Rainey, W. Byrd, J. Shay (1996)
Telomerase activity in human germline and embryonic tissues and cells.Developmental genetics, 18 2
H. Sharma, J. Sokoloski, J. Pérez, J. Maltese, A. Sartorelli, C. Stein, G. Nichols, Z. Khaled, N. Telang, R. Narayanan (1995)
Differentiation of immortal cells inhibits telomerase activity.Proceedings of the National Academy of Sciences of the United States of America, 92 26
G. Allenby, MARIE-THERESE BOCQUELt, Michael SAUNDERSt, S. Kazmer, J. Speck, Michael ROSENBERGERf, A. Lovey, Philippe KASTNERt, J. Grippo, Pierre Chambont, A. Levin (1993)
Retinoic acid receptors and retinoid X receptors: interactions with endogenous retinoic acids.Proceedings of the National Academy of Sciences of the United States of America, 90 1
G. Scholz, I. Pohl, E. Genschow, M. Klemm, H. Spielmann (1999)
Embryotoxicity Screening Using Embryonic Stem Cells in vitro: Correlation to in vivo TeratogenicityCells Tissues Organs, 165
Colin Stewart, I. Gadi, H. Bhatt (1994)
Stem cells from primordial germ cells can reenter the germ line.Developmental biology, 161 2
Jerome Kamm (1982)
Toxicology, carcinogenicity, and teratogenicity of some orally administered retinoids.Journal of the American Academy of Dermatology, 6 4 Pt 2 Suppl
A. Hendrickx (1998)
Teratogenicity of Retinoids in Rodents, Primates and HumansJournal of Toxicological Sciences, 23
A. Wobus, G. Wallukat, J. Hescheler (1991)
Pluripotent mouse embryonic stem cells are able to differentiate into cardiomyocytes expressing chronotropic responses to adrenergic and cholinergic agents and Ca2+ channel blockers.Differentiation; research in biological diversity, 48 3
L. Wang (1990)
[Correlation between protein kinase C and differentiation of HL-60 cells induced by DMSO].Zhongguo yi xue ke xue yuan xue bao. Acta Academiae Medicinae Sinicae, 12 2
M. McBurney, B. Rogers (1982)
Isolation of male embryonal carcinoma cells and their chromosome replication patterns.Developmental biology, 89 2
L. Cocco, S. Capitani, O. Barnabei, R. Gilmour, S. Rhee, F. Manzoli (1999)
Inositides in the nucleus: further developments on phospholipase C beta 1 signalling during erythroid differentiation and IGF-I induced mitogenesis.Advances in enzyme regulation, 39
J. Albanell, Wei Han, Begoña Mellado, R. Gunawardane, Howard Scher, Ethan Dmitrovsky, M. Moore (1996)
Telomerase activity is repressed during differentiation of maturation-sensitive but not resistant human tumor cell lines.Cancer research, 56 7
T. Muramatsu (1988)
Developmentally regulated expression of cell surface carbohydrates during mouse embryogenesisJournal of Cellular Biochemistry, 36
E. Genschow, H. Spielmann, G. Scholz, A. Seiler, N. Brown, A. Piersma, M. Brady, N. Clemann, H. Huuskonen, F. Paillard, S. Bremer, K. Becker (2002)
The ECVAM International Validation Study on In Vitro Embryotoxicity Tests: Results of the Definitive Phase and Evaluation of Prediction ModelsAlternatives to Laboratory Animals, 30
B. Chakravarthy, R. Tremblay, P. Macdonald, V. Krsmanović, J. Whitfield, J. Durkin (1992)
The activation of inactive membrane-associated protein kinase C is associated with DMSO-induced erythroleukemia cell differentiation.Biochimica et biophysica acta, 1136 1
G. Tzimas, H. Buergin, M. Collins, H. Hummler, H. Nau (2007)
The high sensitivity of the rabbit to the teratogenic effects of 13-cis-retinoic acid (isotretinoin) is a consequence of prolonged exposure of the embryo to 13-cis-retinoic acid and 13-cis-4-oxo-retinoic acid, and not of isomerization to all-trans-retinoic acidArchives of Toxicology, 68
S. Bremer, M. Dooren, M. Paparella, E. Kossolov, Bernd Fleischmann, Juergen Hescheler (1999)
Establishment of an Embryotoxicity Assay with Green Fluorescence Protein-expressing Embryonic Cell-derived CardiomyocytesAlternatives to Laboratory Animals, 27
Susanne Bremer, Thomas Hartung (2004)
The use of embryonic stem cells for regulatory developmental toxicity testing in vitro--the current status of test development.Current pharmaceutical design, 10 22
Devendra Kochhar, Heng Jiang, J. Penner, Richard Heyman (1995)
Placental transfer and developmental effects of 9-cis retinoic acid in mice.Teratology, 51 4
E. Kolossov, B. Fleischmann, Qing-Hua Liu, W. Bloch, S. Viatchenko‐Karpinski, O. Manzke, G. Ji, H. Bohlen, K. Addicks, Juergen Hescheler (1998)
Functional Characteristics of ES Cell–derived Cardiac Precursor Cells Identified by Tissue-specific Expression of the Green Fluorescent ProteinThe Journal of Cell Biology, 143
K. Herrmann (1995)
Teratogenic effects of retinoic acid and related substances on the early development of the zebrafish (Brachydanio rerio) as assessed by a novel scoring system.Toxicology in vitro : an international journal published in association with BIBRA, 9 3
Y. Matsushima, E. Kawachi, H. Tanaka, H. Kagechika, Y. Hashimoto, K. Shudo (1992)
Differentiation-inducing activity of retinoic acid isomers and their oxidized analogs on human promyelocytic leukemia HL-60 cells.Biochemical and biophysical research communications, 189 2
D. Solter, B. Knowles (1978)
Monoclonal antibody defining a stage-specific mouse embryonic antigen (SSEA-1).Proceedings of the National Academy of Sciences of the United States of America, 75 11
J. Kraft, Chr. Eckhoff, D. Kochhar, G. Bochert, Ibrahim Chahoud, Heinz Nau (1991)
Isotretinoin (13-cis-retinoic acid) metabolism, cis-trans isomerization, glucuronidation, and transfer to the mouse embryo: consequences for teratogenicity.Teratogenesis, carcinogenesis, and mutagenesis, 11 1
M. Edwards, M. McBurney (1983)
The concentration of retinoic acid determines the differentiated cell types formed by a teratocarcinoma cell line.Developmental biology, 98 1
(1996)
Copyright � 1996, American Society for Microbiology Regulation of Telomerase Activity in Immortal Cell Lines
G. Tzimas, J. Sass, W. Wittfoht, M. Elmazar, K. Ehlers, H. Nau (1994)
Identification of 9,13-dicis-retinoic acid as a major plasma metabolite of 9-cis-retinoic acid and limited transfer of 9-cis-retinoic acid and 9,13-dicis-retinoic acid to the mouse and rat embryos.Drug metabolism and disposition: the biological fate of chemicals, 22 6
J. Garriga, E. Adanero, J. Fernandez-Solà, A. Urbano-Márquez, R. Cussó (2000)
Ethanol inhibits skeletal muscle cell proliferation and delays its differentiation in cell culture.Alcohol and alcoholism, 35 3
J. Kornfehl, A. Temmel, M. Formanek, B. Knerer (1999)
Effects of ethanol treatment of proliferation and differentiation in a head and neck squamous cell carcinoma cell line.Alcoholism, clinical and experimental research, 23 6
E. Lammer (1987)
Teratology Society Position Paper: Recommendations for Vitamin A Use During PregnancyInternational Journal of Toxicology, 6
J. Kraft, B. Löfberg, Ibrahim Chahoud, G. Bochert, Heinz Nau (1989)
Teratogenicity and placental transfer of all-trans-, 13-cis-, 4-oxo-all-trans-, and 4-oxo-13-cis-retinoic acid after administration of a low oral dose during organogenesis in mice.Toxicology and applied pharmacology, 100 1
J. Rohwedel, K. Guan, A. Wobus (1999)
Induction of Cellular Differentiation by Retinoic Acid in vitroCells Tissues Organs, 165
(1987)
Cell culture methods and induction of differentiation of embryonal carcinoma cell lines. Cell culture methods and induction of differentiation of embryonal carcinoma cells
Gabriele Laschinski, Richard Vogel, Horst Spielmann (1991)
Cytotoxicity test using blastocyst-derived euploid embryonal stem cells: a new approach to in vitro teratogenesis screening.Reproductive toxicology, 5 1
A. Arcangeli, L. Ricupero, M. Olivotto (1987)
Commitment to differentiation of murine erythroleukemia cells involves a modulated plasma membrane depolarization through Ca2+‐activated K+ channelsJournal of Cellular Physiology, 132
M. Crettaz, A. Baron, G. Siegenthaler, W. Hunziker (1990)
Ligand specificities of recombinant retinoic acid receptors RAR alpha and RAR beta.The Biochemical journal, 272 2
L. Armstrong, M. Lako, J. Lincoln, P. Cairns, N. Hole (2000)
mTert expression correlates with telomerase activity during the differentiation of murine embryonic stem cellsMechanisms of Development, 97
D. Soprano, K. Soprano (1995)
Retinoids as teratogens.Annual review of nutrition, 15
M. McBurney, E. Jones-Villeneuve, M. Edwards, Peter Anderson (1982)
Control of muscle and neuronal differentiation in a cultured embryonal carcinoma cell lineNature, 299
B. Knowles, D. Aden, D. Solter (1978)
Monoclonal antibody detecting a stage-specific embryonic antigen (SSEA-1) on preimplantation mouse embryos and teratocarcinoma cells.Current topics in microbiology and immunology, 81
M. Heyden, L. Defize (2003)
Twenty one years of P19 cells: what an embryonal carcinoma cell line taught us about cardiomyocyte differentiation.Cardiovascular research, 58 2
P. Morley, J. Whitfield (1993)
The differentiation inducer, dimethyl sulfoxide, transiently increases the intracellular calcium ion concentration in various cell typesJournal of Cellular Physiology, 156
E. Jones-Villeneuve, M. McBurney, K. Rogers, V. Kalnins (1982)
Retinoic acid induces embryonal carcinoma cells to differentiate into neurons and glial cellsThe Journal of Cell Biology, 94
The murine embryonal teratocarcinoma cell line, P19, was genetically manipulated in order to provide preliminary information on compounds that induce differentiation. Without chemical induction, P19 cells remain in an undifferentiated state, but can be induced to differentiate into specific cell types. For example, dimethyl sulphoxide (DMSO) induces cardiac and skeletal muscle differentiation, whereas retinoic acid stimulates neuronal differentiation. P19 cells were transfected with a construct containing a segment of the murineTert (mTert) promoter sequence combined with the green fluorescent protein (GFP) gene, which acts as a reporter gene. mTert expression, the reverse transcriptase component of murine telomerase, is closely linked to telomerase activity and is down-regulated during differentiation. Three retinoids and DMSO induced the differentiation of P19 cells, which was determined by a reduction in mTert_GFP expression, detected by flow cytometry and confocal microscopy as independent methods of detection. A test substance, ethanol, and a control substance, saccharin, did not cause a decrease in mTert_GFP expression. In addition, it could be demonstrated that the mTert_GFP test detects developmentally relevant effects at non-cytotoxic concentrations. The ID50 values derived for the reduction of mTert_GFP expression were lower than the IC50 values detected with the MTT test, by a factor of 21.4 for all-trans retinoic acid, 12.7 for 9-cis retinoic acid, 29.6 for 13-cis retinoic acid, and 8.7 for DMSO. In comparison to the IC50 value for the P19 cell line, a similar IC50 value was obtained with 3T3 cells for ethanol, but there was a 2-fold increase for DMSO. The retinoids were not cytotoxic to 3T3 cells at the concentrations tested. This newly developed test is capable of detecting differentiation-inducing compounds at non-cytotoxic concentrations within 4 days. It offers a method for detecting chemicals with specific toxicological mechanisms, such as the retinoids, which could provide additional information in embryotoxicity testing as different promoters could be employed. Here, we report the use of this novel test system for the successful analysis of DMSO and three retinoids with different in vivo teratogenic potentials.
Alternatives to Laboratory Animals – SAGE
Published: Apr 1, 2005
Read and print from thousands of top scholarly journals.
Already have an account? Log in
Bookmark this article. You can see your Bookmarks on your DeepDyve Library.
To save an article, log in first, or sign up for a DeepDyve account if you don’t already have one.
Copy and paste the desired citation format or use the link below to download a file formatted for EndNote
Access the full text.
Sign up today, get DeepDyve free for 14 days.
All DeepDyve websites use cookies to improve your online experience. They were placed on your computer when you launched this website. You can change your cookie settings through your browser.