Effect of the alkylating agent trisethyleneiminobenzoquinone (Trenimon) on the template activity of chromatin and DNA in RNA and DNA polymerase systems

Abstract

Treatment of chromatin from Ehrlich ascites tumor cells with the alkylating antitumor agent 2,3,5-trisethyleneiminobenzoquinone-1,4 (Trenimon) decreases its template activity in a RNA polymerase system. The inhibition in the template activity of the chromatin is greater after treatment in vivo than after treatment of isolated chromatin with an equivalent concentration in vitro. Deproteinized DNA isolated after in vivo treatment with the alkylating agent shows the same inhibition in template activity as DNA treated in vitro with a corresponding dose. Isolated chromatin treated in vitro exhibits the same sensitivity to the alkylating agent as deproteinized DNA. The difference between the in vivo and the in vitro treated chromatin preparations is not due to an increased ribonuclease activity of the chromatin treated in vivo. Treatment of tumor cells with the alkylating agent at concentrations which inhibit the template activity of the chromatin decreases the capacity of the cells for the puromycin insensitive uptake of acetate into acid soluble nuclear protein. The observed inhibition in the template activity of chromatin in the RNA polymerase system after in vivo treatment with the alkylating agent is interpreted as a modification of the nucleoprotein structure which is not explained by an alkylation of DNA alone. Under the conditions used in our experiments the in vivo as well as the in vitro treatment of the chromatin with the alkylating trisethyleneimino compound Trenimon does not lead to an inhibition of its template activity in a DNA polymerase system.