Summary
Sodium cyanate injected IP at a dose level of 200 or 250 mg/kg caused a 90% or greater inhibition of the incorporation of [3H]thymidine into DNA of B16 melanoma transplanted SC in mice. Despite the inhibitory effect of sodium cyanate on precursor incorporation into DNA, no significant effect on host survival was observed when sodium cyanate was administered as a single agent in the diet, in drinking water, or by IP injection to mice that had received IP transplants of B16 melanoma. The action of melphalan and 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea (CCNU) in prolonging the survival time of melanoma-bearing mice was not enhanced by combined treatment with sodium cyanate. However, combined injections of sodium cyanate and 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) increased the survival of tumor-bearing mice significantly more than injections of BCNU alone at a lower dose than the maximum tolerated one. These data and other studies suggest that B16 melanoma may be less responsive to the action of sodium cyanate than are murine leukemic cells or rat hepatomas.
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References
Allfrey VG, Boffa LC, Vidali G (1977) Selective inhibition with sodium cyanate of protein synthesis in colon cancer cells. Cancer 40:2692–2698
Birch KM, Schütz F (1946) Actions of cyanate. Br J Pharmacol 1:186–193
Boffa LC, Kozak S, Allfrey VG (1981) Activation of sodium cyanate for selective inhibition of protein synthesis in cultured tumor cells. Cancer Res 41:60–66
Burton KA (1956) Study of the conditions and mechanism of the disphenylamine reaction for the colorimetric estimation of deoxyribonucleic acid. Biochem J 62:316–323
Dufour M, St. Germain J, Skalski V, Dorato A, Lazarus P, Panasci LC (1984) Effect of administration of sodium cyanate and melphalan on the lifespan of P388 tumor-bearing CD2Fl mice. Cancer Chemother Pharmacol 12:94–97
Dustin P (1947) Some new aspects of mitotic poisoning. Nature 159:794–797
Herrera-Ornelas L, Petrelli NJ, Madajewicz S, Mittelman A, Allfrey VG (1985) Phase-1 clinical trial of sodium cyanate in patients with advanced colorectal carcinoma. Oncology 42:236–241
Knox P (1976) Carcinogenic nitrosamides and cell cultures. Nature 259:671–673
Labbe RF (1973) Sodium cyanate: chemical properties relevant to sickle cell disease therapy. J Pharm Sci 62:1727–1729
Lea MA, Koch MR (1979) Effects of cyanate, thiocyanate, and amygdalin on metabolite uptake in normal and neoplastic tissues of the rat. J Natl Cancer Inst 63:1279–1283
Lea MA, Parsons J (1981) Effects of cyanate on the distribution of isotope-labeled H2O and extracellular markers in rat liver and tumors. Cancer Res 41:4988–4992
Lea MA, Koch MR, Allfrey VG, Morris HP (1975a) Inhibition by cyanate of DNA synthesis in hepatomas. Cancer Biochem Biophys 1:129–133
Lea MA, Koch MR, Morris HP (1975b) Tumor-selective inhibition of the incorporation of [3H]-labelled amino acids into protein by cyanate. Cancer Res 35:2321–2326
Lea MA, Luke A, Velazquez O, Carpenter L, Martinson CF, Hill HZ, Hill GJ (1985) Action of cyanate on B16 melanoma. Proc Am Assoc Cancer Res 26:321
Moore JV (1985) Dose-response curves after in vivo experimental chemotherapy: Influence of route of administration on biological outcomes. Cancer Chemother Pharmacol 15:91–92
Sariban E, Erickson LC, Kohn KW (1984) Effects of carbamoylation on cell survival and DNA repair in normal human embryo cells (IMR-90) treated with various 1-(2-chloroethyl)-1-nitrosoureas. Cancer Res 44:1352–1357
Wattenberg LW (1981) Inhibition of carcinogen-induced neoplasia by sodium cyanate, tert-butyl isocyanate, and benzyl isothiocyanate administered subsequent to carcinogen exposure. Cancer Res 41:2991–2994
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The work described in this paper was supported by NIH grant CA-35315 and a research award from the Veterans Administration
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Lea, M.A., Luke, A., Velazquez, O. et al. Effects of sodium cyanate in mice bearing B16 melanoma. Cancer Chemother. Pharmacol. 17, 231–235 (1986). https://doi.org/10.1007/BF00256690
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DOI: https://doi.org/10.1007/BF00256690