Motecular and Cellular Radiobiology Project Title: Storage and Transfer of the Genetic Message 15. Relationship ro Other Projects: (Cont‘'d.) RX-03-02-(d) Merigan, Colby at University of Connecticut, and Carter at Johns Hopkins University are working on interferon stimulation and factors affecting interferon. Braun at Rutgers University, and Johnson at University of Michigan are working on the adjuvant action. of polynucleotides on humoral and cell-mediated immunity, Morrell at Upjohn Company, Kalamazoo and Talal at NIH, are studying the effects of polynucleotides on macrophages and on immunity and tolerance. Although some of these investigators work on closely related biological effects, the studies done here and at collaborating laboratories differ importantly in: (1) physical characterization of the polynucleotide complexes; (2) uniqueness of viruses studied, e.g. FMDV only at Plum Island; (3) uniqueness of experimental tumors tested at SloanKettering; (4) comprehensiveness of pharmacology and toxicological studies at Sloan-Kettering; (5) broadness of spectrum of biological effect$ studied with same complexes, 16, Technical Progress in FY 1973: During the past 12 months there has been an increase in thinking and experiment on the interaction of various molecules with nucleic acids and synthetic polynucleotides in collaboration with Drs. Fuller, M. Davies and Pigram, King's College, This has arisen as a reverse spin-off from efforts to decrease the biodegradability of synthetic polynucleotides in vivo by complexing them with other molecules and also because of increased interest in how environmental pollutants, e.g. polynuclear hydrocarbons, may damage by complexing with nucleic acids, Since intercalation--an interaction whereby the planar portion of a molecule slips in between adjacent base-pairs™ in double-helical DNA--is widely assumed to be an important mechnaism of the action of many basic drugs, e.g. acriflavin, ethidium, etc,, but rigorous proof has been lacking hitherto and models have been ambiguous, action of daunomycin with DNA was reviewed further, the inter- Daunomycin--a glycosidic anthracycline antibiotic widely used for the palliation of acute leukemia and solid tumors in man--is a molecule of considerable biological interest, Its biological activity seems to be due to complex formation with DNA, Evidence for the first time from both x-ray diffraction and molecular model-building studies have provided data on the stereochemistry of intercalation into DNA of daunomycin. These are the first gtudies to present detailed x-ray evidence that intercalation of a chemi into DNA is occuring and to give accurately the degree of untwisting of t molecule--an inevitable consequence of intercalation--per moleew¥@ of bound intercalated chemical. There are many references in the literature, particularly on circular DNA, to the paper by Fuller and Waring (Bunsengesellschaft flr Physiklische Chemie, 68, 805, 1963), where a value for this important parameter--i,e, the untwisting of DNA--was proposed. (See Continuation Sheet) 1419313 RX- 253