The aim of the proposed investigation is to study the mechanism of action of the antitumor agent adriamycin, its analogs 4'-epi-adriamycin, the beta-anomer of adriamycin, and N-trifluroacetyladriamycin-14-valerate (AD-32). Adriamycin is believed to be carcinostatic because it binds to DNA, presumably by intercalation, and thus inhibits nucleic acid synthesis. 4'-epi-adriamycin like adriamycin binds to DNA but is less toxic than adriamycin and has better antitumor activity. The beta-anomer of adriamycin. AD-32 exhibits significantly greater antitumor activity than adriamycin and less toxicity, does not bind to DNA in vitro but it may do so in vivo. It is proposed to study the mechanism of action of these compounds by studying their effects on the physical-chemical properties of DNA and chromatin and to investigate their effects on transcription in nuclei, chromatin, and DNA of L1210 cells utilizing L1210 cells utilizing L1210 RNA polymerase II. These studies are designed to gain information as to the mechanism of action of these compounds under both in vitro and in vivo conditions.
NIH ExPorter
NIH ExPorter