Drug action and chromatin structure. I. Adriamycin binding to core particle of nucleosomes and subsequent enhanced DNA fragmentation induced by micrococcal nuclease.

The relevance of the subunit structure of chromatin to the mode of action of Adriamycin in Novikoff hepatoma had been investigated. To elucidate whether drug binding takes place at random along the chromatin fiber or not Novikoff hepatoma nuclei treated with Adriamycin in vivo were digested with Micrococcal nuclease and were subsequently separated into three fractions, S1, S2 and P2. In these chromatin fraction Adriamycin and the DNA content was determined. DNA were isolated from the above fractions and were analyzed by polyacrylamide gel electrophoresis, furthermore the S2 fraction was sedimented on sucrose density gradient. The results indicate that binding of Adriamycin takes place preferentially on the core particle inducing structural alterations. Adriamycin binding not only enhanced DNA nuclease digestion but altered the size of the fragments.