Project Title: 14. Scope: Molecular and Cellular Radiobiology Storage and Transfer of the Genetic Message RX-03-02-(d) (Cont'd.) effects such as oncogenesis, the long-range objectives stated above were established. The import of work in many laboratories is to assign a clearer role to viruses and chemicals found in the environment, which, in addition to radiation, may be genetically damaging and often oncogenic. The environmental hazards for oncogenesis require a more general knowledge of the interaction of viruses, chemical agents, and radiation. For the long-term objective of assessing environmental hazards, it is necessary to arrive at how the physical structure of informational macromolecules is affected by a wide variety of chemicals, viruses, and physical agents, Control of protein synthesis by nucleic acids continues to be the central target, Despite advances, it is likely to remain central at least until the structure of ribosomes and transfer RNA molecules, interaction and control are elucidated. etc, ‘and their Despite world-wide expansion of research on this subject, further nucleic acid protein studies will be needed for decades before intracellular regulation in higher organisms is understood, As these factors are sorted ouc, there is a widely recognized need to integrate the interactions of all these environmentally damaging agents: viruses, chemicals and radiation, Study of che interaction of chemicals with the informational macromolecules needs extension and entails. expanded research on the macromolecules, themselves and of the enzymes involved in their own synthesis and protein , synthesis generally. These interactions are central to understanding how factors in the environment influence heredity and distort differentiation. They also relate to how viruses, chemicals and radiation induce somatic mutation, and how they and other factors accelerate aging. The approach to a precise understanding of how radiation and chemical pollutants induce effects such as oncogenesis and genetic mutation is being made in this program in several diverse but complementary and directly interrelated ways: (1) In collaboration with the Biophysics Department and MRC Unit at King's College, London (with Professor M,H,F. Wilkins and Drs. W. Fuller and W.J. Pigram), the 3-dimensional structure of natural double-stranded RNA's and of synthetic polynucleotides and of their complexes with other molecules, such as histones and novel chemicals is studied. These complexes are studied not only because of their potential increase in the biological effectiveness of these molecules but also because of the light they gaighe throw on the interaction and control of the informational macro- molegmies (for which the synthetic polynucleotides may be considered models). The s@#agtudies should thus assist in defining the targets of environmental damage and help understand the possible synergistic effect of environmental chemicals in promoting this damage with radiation, (2) In collaboration with Dr, E. Popenoe (this Department), the role of RNA-dependent DNA polymerase is studied in proliferating normal, stimulated cells... tumor, and immunologically Using poly (rA°dT) as a primer it has been possible to (See Continuation Sheet) bi V93td RX- 250