Effects of 4-nitro- and 4-sulpho-7-substituted benzofurazans on nucleic acid and protein synthesis of a malignant fibrosarcoma cell line in combination with mild hyperthermia.

The inhibitory effects of substituted nitro- and sulphobenzofurazans on DNA, RNA and protein synthesis were compared in a new malignant fibrosarcoma cell line at 37 degrees C and 41 degrees C. The effects of these drugs with and without mild hyperthermia were evaluated by determining the % inhibition of incorporation of 3H-precursors into DNA, RNA and protein. None of the sulphobenzofurazan derivatives (Sbf) were effective inhibitors of nucleic acid and protein synthesis at 37 degrees C nor did they enhance the inhibitory effect of hyperthermia alone. The nitrobenzofurazan derivatives (Nbf) at concentrations 10% that used for the Sbf derivatives strongly inhibited biopolymer synthesis in a dose related manner; 4-chloro-7-nitrobenzofurazan (Nbf-Cl) being the most potent inhibitor. Hyperthermia amplified the effect of all the Nbf compounds tested on RNA and protein synthesis but did not further affect DNA synthesis. This selective synergistic effect was most pronounced when the lowest concentrations of Nbf compounds were studied. The synergism however, did not follow a uniform pattern. 6-Mercaptopurine and 6-(1-methyl-4-nitro-5-imidazoyl)thiopurine (Azathioprine) (100 microM) had marginal effects on nucleic acid and protein synthesis when the cells were exposed to these two thiopurines for 1 h at both 37 degrees C and 41 degrees C and they had only a moderate inhibitory effect after exposure for 15 h.