Studies related to antitumor antibiotics. Part IX. Reactions of carzinophillin with DNA assayed by ethidium fluorescence

Publisher Website
Google Scholar
Abstract
Reactions of the antitumor antibiotic carzinophillin (CA) with native [calf thymus] DNA and synthetic polynucleotides were examined by an ethidium fluorescence assay. CZ rapidly produces covalent linkage of the complementary strands of a variety of DNA without activation. This process is accompanied by extensive alkylation, as detected by reduced fluorescence due to destruction of potential intercalation sites for ethidium. These processes which occur without loss of purine or pyrimidine bases show a preference for bonding to guanine groups (but not at the N-7 position). Examination of the reversibility of the cross links suggests they involve 1 permanent link to guanine and a 2nd weaker linkage, possibly to a cytosine residue. Cross linking and alkylation show strong pH dependence and are favored at lower pH, suggesting that reactive sites on the antibiotic are basic. The addition of intercalating agents to DNA before treatment with CZ inhibits cross linking.