[en] In the present study we examined the ultrastructural modifications as well as the precise distribution of DNA and RNA in RT4 cell nucleoli following a 3-h exposure to nontoxic or toxic doses of ametantrone (AMT), poly(adenylate-uridylate) (polyr(A-U), or an AMT/polyr(A-U) combination. While distribution of nucleic acids within the various nucleolar components is not modified following all treatments, the nucleoli exhibit several ultrastructural changes: redistribution of the nucleolar components, decrease in the number of fibrillar centers, and increase in the size of the fibrillar centers. The relative frequencies of the test agents to induce the apparition of nucleoli of compact type are AMT/polyr(A-U) > AMT approximately polyr(A-U) > sham-treated, while the abilities of the test agents to induce the nucleolar segregation are AMT/polyr(A-U) approximately AMT > polyr(A-U) > sham-treated cells. These ultrastructural changes are characteristics of drugs that intercalate into DNA and inhibit rDNA transcription as well as rRNA processing and release of nascent preribosomes from the nucleolus.
1. Parker, S. L., Tong, T., Bolden, S., and Wingo, P. A. (1996) CA Cancer J. Clin. 65, 5-27.
2. Jocham, D., Beer, M., Baumgartner, R., Staehler, G., and Unsold, E. (1989) Ciba Found. Symp. 146, 198-208.
3. Shipley, W. U., Prout, G. R., and Kaufman, D. S. (1990) Cancer 65, 675-683.
4. Prout, G. R., jr., Lin, C-W., Benson, R. C., Nseyo, U. O., Daly, J. J., Griffin, P. P., Kinsey, J., Tian, M., Lao, Y., Mian, Y., Chen, X., Ren, F., and Qiao, S. (1987) N. Engl. J. Med. 317, 1251-1255.
5. Sehgal, P. B., Tamm, I., and Vilcek, J. (1975) J. Exp. Med. 142, 1283-1300.
6. De Clercq, E., and Torrence, P. F. (1977) J. Gen. Virol. 37, 619-623.
7. Jamison, J. M., Krabill, K., Flowers, D. G., and Tsai, C-c. (1990) Life Sci. 46, 653-661.
8. Jamison, J. M., Bonilla, P. J., and Tsai, C-c (1990) Antiviral Chem. Chemother. 1, 53-60.
9. Jamison, J. M., Krabill, K., Flowers, D. G., and Tsai, C-c. (1990) Cell Biol. Int. Rep. 14, 219-228.
10. Jamison, J. M., Krabill, K., Flowers, D. G., and Tsai, C-c. (1990) Biochimie 72, 235-243.
11. Jamison, J. M., Krabill, K., Hatwalkar, A., Jamison, E., and Tsai, C-c. (1990). Cell Biol. Int. Rep. 14, 1075-1084.
12. Jamison, J. M., Bonilla, P. J., and Tsai, C-c. (1990). Antiviral Chem. Chemother. 1, 285-292.
13. Jamison, J. M., Krabill, K., Allen, K. A., Stuart, S. H., and Tsai, C-c. (1990). Antiviral Chem. Chemother., 1, 333-347.
14. Gilloteaux, J., Jamison, J. M., and Summers, J. L. (1993) J. Scanning Microsc. 15, 55-56.
15. Jamison, J. M., Summers, J. L., and Gilloteaux, J. (1993) in Proc. 51st Annual Meeting of the Microscopy Society of America, Cincinnati, Ohio (Bailey, G. W., and Reider, C. L., Eds.), pp. 196-197, San Francisco Press, San Francisco.
16. Jamison, J. M., Gilloteaux, J., and Summers, J. L. (1993) Cell Biol. Int. Rep. 17, 1091-1105.
17. Mahler, R. R., and Perlman, P. S. (1972) Arch. Biochem. Biophys. 148, 115-129.
18. Murdock, K. C., Child, R. G., Fabio, P. F., Angier, R. B., Wallace, R. E., Durr, F. E., and Citarella, R. V. (1979). J. Med. Chem. 22, 1024-1030.
19. Kuhn, J. G., Balmer, C. E., Ludden, T. M., Loesch, D. M., Von Hoff, D. D., Bender, J. F., and Grillo-Lopez, A. J. (1987) Cancer Chemother. Pharmacol. 19, 133-137.
20. Kapuscinski, J., and Darzynkiewicz, Z. (1986) Proc. Natl. Acad. Sci., USA 83, 6302-6306.
21. Kapuscinski, J., Darzynkiewicz, Z., Traganos, F., and Melamed, M. R. (1981) Biochem. Pharmacol. 30, 231-240.
22. Thiry, M. (1992) J. Histochem. Cytochem. 40, 411-419.
23. Thiry, M. (1992) Nucleic Acids Res. 20, 6195-6200.
24. Puvion-Dutilleul, F., Mazan, S., Nicoloso, M., Pichard, E., Bachellerie, J-P., and Puvion, E. (1992) Eur. J. Cell Biol. 58, 149-162.
25. Mikhaylova, V. T., Thiry, M., Stephanova, E., Goessens, G., and Markov, D. V. (1996) Exp. Cell Res. 225, 389-398.
26. Busch, H., and Smetana, K. (1970) The Nucleolus, Academic Press, New York.
27. Smetana, K, and Busch, H. (1974) in The Cell Nucleus (Busch, H., Ed.), Vol. 1, pp. 73-147, Academic Press, New York.
28. Goessens, G. (1978) J. Ultrastruct. Res. 65, 83-89.
29. Jordan, E., and Mc Govern, J. (1981) J. Cell Sci. 52, 373-389.
30. Altmann, G., and Leblond, C. (1982) J. Cell Sci. 56, 83-99.
31. Medina, F., Risueno, M., and Moreno Diaz de la Espina, S. (1983) Biol. Cell 48, 31-38.
32. Goessens, G. (1984) Int. Rev. Cytol. 87, 107-158.
33. Schell, P. L. (1971) Biochim. Biophys. Acta 240, 472-484.
34. Marin, J. G., Rodrigue, J. M., Mencia-Huerta, P. E., and Braquet, P. (1993) Biochim. Biophys. Acta 1178, 103-110.
35. Chapekar, M. S., Knode, M. C., and Glazer, R. I. (1988) Mol. Pharmacol. 34, 461-466.
36. Johnson, R. K., Zee-Cheng, R. K. Y., Lee, W. W., Acton, E. M., Henry, D. W., and Cheng, C. C. (1979) Cancer Treat. Rep. 63, 425-439.
37. Kapuscinski, J., and Darzynkiewicz, Z. (1985) Biochem. Pharmacol. 34, 4203-4213.
38. De Clercq, E., Wells, R., Grant, R., and Merigan, T. (1971) J. Mol. Biol. 56, 83-100.
39. Iliescu, R., Repanovici, R., Mutiu, A., Shanazarov, N., Danielescu, G., Popa, L. M., and Cajal, N. (1983) Rev. Roum. Med. Virol. 34, 191-196.
40. Jamison, J. M., Gilloteaux, J., and Summers, J. L. (1994) Prog. Mol. Subcell. Biol. 14, 89-113.
41. Simard, R., Langelier, Y., Rosemonde, M., Maestracci, N., and Royal, A. (1974) in The Cell Nucleus (Busch, H., Ed.), Vol. 3, pp. 447-487, Academic Press, New York.
42. Fakan, S., and Puvion, E. (1980) Int. Rev. Cytol. 65, 255-299.
43. Hadjiolov, A. A. (1985) in The Nucleolus and Ribosome Biogenesis, Cell Biology Monographs (Alfert, M. et al., Eds), Vol. 12, pp. 165-196, Springer-Verlag, Wien.
44. Escande-Geraud, M., Azum, M., Tichadou, J., and Gas, N. (1985) Exp. Cell Res. 161, 353-363.
45. Buckwalter, C. A., Liu, A. H., Tanizawa, A., Pommier, Y. G., Cheng, Y. C., and Kaufmann, S. H. (1996) Cancer Res. 56, 1674-1681.
46. Desnoyers, S., Kaufmann, S. H., and Poirier, G. G. (1996) Exp. Cell Res. 227, 146-153.
