The effect of dibromodulcitol on the template activity of DNA chromatin and nuclei from Yoshida sarcoma cells.
It has been shown earlier that after in vivo administration, dibromodulcitol (DBD) reacts with DNA and to a greater extent with chromosomal proteins of Yoshida sarcoma cells. The present experiments were designed to show if the binding of DBD to the chromatin elements of Yoshida sarcoma cells causes any changes in RNA synthesis using either DNA or chromatin as template in bacterial RNA polymerase system. During 4 to 24 h following in vivo administration, DBD reduces the template activity of dna without detectable single-strand breaks in the template DNA in alkaline sucrose gradients. Using chromatin as template the same dose of DBD produces no or very slight inhibition of RNA synthesis. Measuring the DNA-dependent RNA synthesis in nuclei isolated from Yoshida cells of treated rats, the dose of DBD which markedly inhibited the template activity of DNA, resulted in a significant stimulation of the nuclear RNA synthesis. The increased RNA synthesis was not due to an inhibition of ribonuclease activity. The observed alterations of the transcriptive properties of chromatin and nuclei produced by DBD are interpreted as being due to a modification of the whole nucleoprotein structure caused by the interaction of DBD with both DNA and chromosomal proteins.