Project Title: 16, Molecular and Cellular Radiobiology Storage and Transfer of the Genetic Message Technical Progress in FY 1973: (Cont'd,) RX-03-02-(d) recognizable and lethal leukemia-lymphoma in AKR mice, Consideration is being given to the possibility of beginning the treatment at an earlier age since evidence from other viruses indicates that polynucleotides are more effective when given prophylactically; also to more intensively sequential dosage schedule: To understand how polynucleotides and other interferon inducers work with a view to increasing their biological effectiveness, approaches have been used, several in vitro Preliminary experiments indicate that the addition of poly (rI*rC) to the antigen, bovine serum albumin (BSA) added to lymphocytes incubated in vitro from mice previously exposed to BSA antigen in vivo, Significantly increased lymphocyte transformation compared to that after exposure to BSA alone. These studies are being extended. In cultures of HeLa S-3 ceils, synchronized with amethopterin and adenosine followed by release of the block with thymidine, poly(rIerC) and poly(rA-rU) significantly inhibited DNA synthesis in S phase cells (730%) with no effect on protein and RNA synthesis, Poly(rI+:rC) had no effect on DNA synthesis in log phase cells, This highly specific finding is being followed up; it is important noc only for understanding the way in which synthetic polynucleotides induce their effects but may prove to be a significant probe to understanding further, the details of DNA synthesis, The collaborative studies with Dr. reported in RX-03-02-(a). 17. E. A. Popenoe of this Department are Expected Results in FY 1974: It is still hoped to complete papers on the high-resolution data and refinement of B DNA and on the complex of poly(dA:rU); as indicated pre- viously, completion of these papers depends on the cooperation of research collaborators, The large paper on intercalation vs. external binding of drugs to DNA (in preparation over several years with Drs, Fuller and Pigram) needs some additional Fourier transform compilations including a program of calculation on the packing of molecules, It is hoped that this can be completed within the next 12 months. Further experimental work on the interaction of ethidium bromide and DNA will be carried out to obtain evidence, if possible, on the increase of layer-line spacing with increased bound drug analogous to the findings with daunomycin and DNA. Studies on che interaction of actinomycin and DNA will be extended by maintaining fibers of the comp ac very high humidity in an effort to favor the intercalation type of bMding and obtain clear evidence for intercalation in this complex. Further x-ray diffraction studies will be made of complexes of poly(rlerC) and poly(rA-rU) with polyarginine and polylysine to illuminate the structure of nucleohisctone and hence of the chromosome, (See Continuation Sheet) bE VS3t1 If the data from these model RX-257