Project Title: 13. Biclogical Studies of Materials Arising from Energy Operations Interaction of Chemicals with Nucleic Acids Publications: RX-93-06-(b) Project not yet initiated. ~4, Scope: A) 200 Word Summary One of the long-range effects of non-nuclear energy systems urgently needing analysis is carcinogenesis (oncogenesis). This involves more than the direct effect in present generations since there is the possibility of genetic damage, Chemical carcinogens given at low doses over long periods of time present the same problem as do low doses of radiation at low dose rates: one has to extrapolate experience from high to low doses, Since the hazard from low doses of common pollutants generated by non-nuclear energy sources would only be deducible from a precise understanding of how these pollutants induce effects, studies are needed on how such environmental contaminants interact with the informational macromolecules, that ts to say, nucleic acids, This approach offers the opportunity not only of understanding how toxic chemicals induce biological damage, but may also indicate ways to minimize damage. As knowledge of these interactions increases, it may serve as a rapid detection system for chemicals likely to cause genetic damage and tumors, The aim of this study is prediction, not description--to tell before the fact what kinds of molecule are likely to cause intense pharmacological effects, notably oncogenesis and genetic effects. B) Supplement to 200 Word Summary: A survey will be made of soluble carcinogens (soluble in physiological solution) apart from polynuclear hydrocarbons--emitted from fossil-fuel power generating plants, and of soluble carcinogens--apart from polynuclear heterocyclic compounds and polynuclear aromatic hydrocarbons--present in urban atmosphere, Chemicals recognized as directly carcinogenic will be complexed with DNA, double-stranded RNA, and synthetic RNA so as to detect their exact points of interaction, The interaction of the carcinogens in highly specific ways with the DNA and RNA will be followed spectrophoto- metrically, by melting-curve analyses, and, when indicated by ultracentrifugation analyses. Im critical cases, x-ray diffraction studies will be made of fibemm. of complexes and the data from these combined with molecular modelbui ® to provide rigorous proof on the stereochemistry of the interaction of ¢hemical with the nucleic acid, 15, Relationship to Other Projects: The proposed program extends to environmental pollutant studies on the interaction of drugs with nucleic acids carried out under budget activity (See Continuation Sheet) 11193249 RX - 386