Embryonic carcinoma

Imidazole antimycotics, ketoconazole, clotrimazole, and miconazole are potent inhibitors of various cytochrome P450-isoenzymes that also affect the metabolism of retinoids. They were fust shown to inhibit the metabolism of RA in F9 embryonal carcinoma cells. When tested in vitm liarazole, a potent CYP-inhibitor, suppressed neoplastic transformation and upregulated gap junctional communication in murine and human fibroblasts, which appeared to be due to the presence of retinoids in the serum component of the cell culture medium. Furthermore, liarazole magnified the cancer chemopreventive activity of RA and (3-carotene in these experiments by inhibiting RA-catabolism as demonstrated by absence of a decrease in RA-levels in the culture medium in the presence of liarazole over 48 h, whereas without liarazole 99% of RA was catabolized. In vivo, treatment with liarazole and ketoconazole reduced the accelerated catabolism of retinoids and increased the mean plasma all-irans-RA-concentration in patients with acute promyelocytic leukemia and other cancels. 

Embryonal carcinoma cell lines have also been established in culture from transplantable teratocarcinomas. The embryonal carcinoma (EC) stem cells present in the tumors actually differentiated, and give rise to a variety of different types of embiyonic and adult cells. When these EC cells are cultured, they still possess the... 

F9 embryonal carcinoma cells have a simple set of growth supplements which are required for growth in serum-free medium insulin, transferrin, and fibronectin (Rizzino and Sato, 1978). Fibronectin is a component of the extracellular matrix and facilitates the attachment of the cells to the culture dish. In addition, high density lipoprotein (HDL) has been observed to promote the growth of F9 cells serum-free. 

Rizzino, A.A. Sato, G. (1978). Growth of embryonal carcinoma cells in serum free medium. Proc. Natl. Acad. Sci. USA 75, 1844-1848. 

Simeone, A., Acampora, D., Arcioni, L., Andrews, P. W., Boncinelli, E., and Mavilio, F. (1990). Sequential activation of HOX 2 homeobox genes by retinoic acid in human embryonal carcinoma cells. Nature 346 763-766. 

Advances in cell culture techniques have allowed the use of trophoblast cell cultures to evaluate the various transporter and metabolic systems of the placenta. Many studies have used primary cultures of undifferentiated cytotro-phoblasts isolated from placentas, whereas others have used trophoblast cell lines as a model. Trophoblast cell lines can be generated from normal tissues or malignant tissues and also from embryonal carcinomas exhibiting trophoblast differentiation [48],... 

Injection of zinc chloride solution into the testes of 49 Syrian hamsters resulted in areas of necrosis occupying about 25% of each testis two embryonal carcinomas of the testis were found 10 weeks later at necropsy/ There is no evidence that zinc compounds are carcinogenic after administration by any other route/... 

Guthrie J, Guthrie OA Embryonal carcinomas in Syrian hamsters after intratesticular inoculation of zinc chloride during seasonal testicular growth. Cancer Res 34 2612-2613, 1974... 

The implementation of animal test protocols in the 1980s has been accompanied by the development of a host of alternative methods to study adverse effects of chemicals on reproductive and developmental parameters. For example, rat whole embryo culture stems from the seventies (16), as does the rat limb bud organ culture (17) and rat limb bud and brain micromass was developed in the eighties (18). An elegant nonvertebrate alternative model used regeneration of polyps of Hydra atUnuata from dissociated cells (19). Animal-free in vitro alternatives include those employing the proliferation of a human embryonic palatal mesenchymal cell line (20), the attachment of a mouse ovarian tumor cell line (21), and the differentiation of a neuroblastoma cell line (22) and a embryonal carcinoma cell line (23). Various overviews of methods have been published over the years (24). The predictability of... 

Kondo K, Tsuneizumi K, Watanabe T, Oishi M. Induction of in vivo differentiation of mouse embryonal carcinoma (F9) cells by inhibitors of topoisomerases. Cancer Res. 50, 5398-5404, 1991. 

Hennemann H, Schwarz J, Willecke K Characterization of gap junction genes expressed in F9 embryonic carcinoma cells Molecular cloning of mouse connexin31 and -45 cDNAs. Eur J Cell Biol 1992a 57 51-58. 

Targeted delivery has also been used to investigate the structure of carbohydrates needed to obtain discrimination of cellular uptake between liver and tumor cells [184], A study was performed by doubly modifying BSA with both a fluorophore (via Lys isothiocyanate derivatization) and different fucose derivatives (via Tyr diazotization). Similar studies have used EDC-mediated coupling to also attach therapeutic agents for delivery to human embryonal carcinoma cells [185]. 

In Table 6-2, peak intensities of the three types of tissues are compared. It is seen that the intensities at 1,039 and 1,076 cm-1 increase in going from normal to cirrhotic to cancerous tissues. The same trend is seen in the intensity ratio of the 1,182/1,156-cm-1 bands. Since RBC contributions to these two bands are similar, this ratio can also be used for cancer diagnosis. The increased intensity of the 1,182-cm-1 band may indicate an increase in production of a-fetoprotein, which is a specific antigen for hepatoma and embryonal carcinoma. The band at 1,039 cm-1 may be due to the phenylalanine residue. Finally, the band at 1,076 cm-1 is due to the symmetric PO2 vibration of the DNA backbone (Section 4.1.2), and its increase in Raman intensity indicates an increase in the DNA concentration in cancer tissues. 

B. Roy, R Taneja, and P. Chambon. Synergistic activation of retmoic acid (RA)-responsive genes and induction of embryonal carcinoma cell differentiation by an RA receptor alpha (RAR alpha)-, RAR beta-, or RAR gamma-selective ligand in combination with a retinoid X receptor-specific ligand. Mol Cell Bid, 15 (12), 6481-6487, 1995. 

H. Chiba, J. Clifford, D. Metzger, and P. Chambon. Distinct retinoid X receptor-retinoic acid receptor heterodimers are differentially involved in the control of expression of retinoid target genes in F9 embryonal carcinoma cells. Mol Cell Bid, 17 (6), 3013-3020, 1997. 

Song Y, Withers DA, Hakomori S. Globoside-dependent adhesion of human embryonal carcinoma cells, based on carbohydrate-carbohydrate interaction, initiates signal transduction and induces enhanced activity of transcription factors API and CREB. J. Biol. Chem. 1998 273 2517-2525. 

Eggens 1, Fenderson B, Toyokuni T, Dean B, Stroud M, Elakomori 35. S. Specific interaction between Le-x and Le-x determinants. A possible basis for cell recognition in preimplantation embryos and in embryonal carcinoma cells. J. Biol. Chem. 1989 264 9476-9484. 

Fluorescence microphotolysis can be used to measure diffusion in single cellsand nuclear envelope permeability. Pyranine probes have been used to measure internal pH changes in Escherichia coli membrane vesicles. Probe measurements of intralysosomal pH in living cells and perturbation of pH has been described by Ohkuma and Poole.Fluorescence polarization of six membrane probes in embryonal carcinoma cells have been measured by a cell sorter,Fluorescence of pancreatic islets labelled with fluorescein diacetate has been used to show the effects of cations, ionophores, and hypoglycaemic sulphonylureas. ... 

Cotte, C., Raghavan, D., McDhinney, R. A. and Monaghan, R (1982). Characterization of a new human cell line derived from a xenografted embryonal carcinoma, fri Vitro 18,139-149. 

Rusciano, D., Lorenzoni, P. and Burger, M. M. (1991). The role of both specific cellular adhesion and growth promotion in fiver colonization by F9 embryonal carcinoma cells. Int. J. Cancer 48, 450-456. 

Terrana, B., Rusciano, D. and Pacenti, L. (1987). Organ colonization pattern of retinoic acid-treated and -untreated mouse embryonal carcinoma F9 cells. Cancer Res. 47, 3791-3797. 

Roy, B., Taneja, R., and Chambon, P. (1995). Synergistic activation of retinoic acid (RA)-re-sponsive genes and induction of embryonal carcinoma ceU differentiation by an RA receptor a (RARa)-, RARP-, or RARy-selective ligand in combination vdth a retinoid X receptor-specific ligand. Mol. Cell. Biol. 15, 6481-6487. 

---