Summary
Several drugs, containing a halogen atom, F or Br, that are being used in antiviral or anticancer therapy, were studied for their localization in cultured cells by ion microanalysis. The association allows to reduce the exposure time to define the intracellular localization of the studied element. The topography of the cells is given by the image of the polyatomic ion 26CN−. The image of the distribution of 81Br− or 19F−, coded in another color scale, can be superimposed, giving a polychromic image of the cell, thus showing the intracellular localization of the compound. MCF-7 tumor cells were cultured in the presence of pyrimidine derivatives. 5-Bromo-2′-deoxyuridine (BUdR) and 5-trifluorothymidine (F3TdR) were localized in the nucleus, 5-fluoro-2′-deoxyuridine (FUdR) in the nucleus and only in some nucleoli. The method is simple and rapid, as compared with techniques using radiolabeled compounds, or with immunocytochemical techniques. It is possible to observe two different compounds in the same cell. It could be applied to other compounds containing a halogen atom.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Berry JP, Poupon MF, Galle S, Escaig F (1984) Role of lysosomes in gallium concentration by mammalian tissues. Biol Cell 51:43–52
Berry JP, Escaig FL, Ange F, Galle P (1986) Methods in laboratory Investigation Ion Microscopy of the Thyroid Gland: A method for imaging stable and radioactive iodine. Lab Invest 55:109–119
Chassard Bouchaud C (1987) Current trends and applications of secondary ion microscopy in medicine and biology. In: Benninghoven A, Huber AM, Werner HW (eds) SIMS VI. John Wiley, New York, pp 855–861
Cavellier JF, Berry JP, Escaig F, Boumati P, Gaume P (1989) Processing of secondary ion microscope images. An example of application to the thyroid. J Microsc 154:37–39
Droz B, Bouteille M, Sandoz D (1976) Techniques in radioautography. J Microsc Biol Cell 27:71–296
Fakan S (1978) High resolution autoradiography studies on chromatin functions. In: Busch H (ed) The cell nucleus. Academic Press, New York, pp 3–53
Fujiwara Y, Oki T, Heidelberger C (1969) Fluorinated pyrimidines. Mol Pharmacol 6:273–280
Galle P (1984) Tissue localization of isotopes by ion microscopy and microradiography. In: Benninghoven A, Okano J, Simizu R, Werner HW (eds) SIMS IV. (Springer Series in Chemical Physics, vol 36). Springer, Berlin Heidelberg New York, pp 495–497
Galle P, Berry JP (1986) Analytical ion microscopy of cells and tissues. In: Feder R, McGowan JW, Shinozaki DM (eds) Examining the submicron world. Plenum Press, New York, pp 35–50
Goodman LS, Gilman A (1980) The pharmacological basis of therapeutics. In: Goodman LS, Gilman LA (eds) Pyrimidines analogs. MacMillan, New York, pp 1276–1282
Harms G, van Goor H, Koudstaal J, de Ley L, Hardonk MJ (1986) Immunohistochemical demonstration of DNA incorporated 5-bromodeoxyuridine in frozen and plastic embedded sections. Histochemistry 85:139–143
Heidelberger C (1975) Fluorinated pyrimidines and their nucleosides. In: Sartorelli AC, Johns DG (eds) Antineoplastic and immunosuppressive agents. (Handbook of Experimental Pharmacology, vol 38/2). Springer, Berlin Heidelberg New York, pp 193–231
Heidelberger C, King DH (1979) Trifluorothymidine. Pharmacol Ther 6:427–442
Hindie E, Escaig F, Coulomb B, Lebreton C, Galle P (1989) The localization of carbon 14 labeled molecules in biological samples by ion mass microscopy. J Histochem Cytochem 37:135–138
Kjellen L (1962) Effect of 5-halogenated pyrimidines on cell proliferation and adenovirus multiplication. Virology 18:64–70
Kufe WD, Major PP, Egan M, Loh P (1981) 5-fluoro-2′-deoxyuridine incorporation in L 1210 DNA. J Biol Chem 256:8885–8888
Morstyn G, Hsu SM, Gratner H, Russo A (1983) Bromodeoxyuridine in tumors and chromosomes detected with a monoclonal antibody. J Clin Invest 72:1844–1850
Roobol C, Dobbeleer GBE, Bernheim JL (1984) 5-fluoro-uracil and 5-fluoro-2′-deoxyuridine follow different metabolic pathways in the induction of cell lethality in L 1210 leukemia. Br J Cancer 49:739–744
Sugihara H, Hattori T, Fukuda M (1986) Immunohistochemical detection of bromodeoxyuridine in formalin-fixed tissues. Histochemistry 85:193–195
Umeda M, Heidelberger C (1968) Fluorinated pyrimidines XXX. Comparative studies of fluorinated pyrimidines with various cell lines. Cancer Res 28:2529–2538
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Berry, J.P., Lespinats, G., Escaig, F. et al. Intracellular localization of drugs in cultured tumor cells by ion microscopy and image processing. Histochemistry 93, 397–400 (1990). https://doi.org/10.1007/BF00315857
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00315857