Comparison of properties of the in vitro and cellular anthramycin-DNA adducts and characterization of the reaction of anthramycin with chromatin

The reaction of anthramycin with DNA has been examined to determine the chemical identity of the adduct which forms in a living cell and to observe the effects of the nucleosome structure of chromatin on drug binding. The chemical identity of the cellular adduct was probed by comparing various properties of the cellular adduct to properties of the known, in vitro adduct. The effect of the histones on anthramycin binding was investigated by time-course binding reactions. Results indicate that the properties of the cellular anthramycin-DNA adduct are similar to the in vitro adduct. The histone proteins associated with DNA in chromatin were found to decrease both the reaction kinetics and the final levels of anthramycin binding. Anthramycin reacts appreciably with nucleosome core DNA, but appears to exhibit a preference for linker DNA.