The central objective of this study is to identify and characterize the reaction products of the polycyclic aromatic carcinogens with DNA, both in vivo and vitro. Two parallel avenues of approach are utilized: (1) Polycyclic carcinogens such as benzo(a)pyrene and benzo(e)pyrene are added to cells in tissue culture. After incubation, the DNA and RNA fractions are analyzed and the nature of the covalent carcinogen-nucleic acid adducts are analyzed by a combination of spectroscopic and high pressure liquid chromatography techniques. (2) Synthetically prepared diolepoxide derivatives of these same polycyclic molecules are reacted with nucleic acids. The physico-chemical and structural properties of these covalent adducts are then compared with those obtained from cells in tissue culture, allowing for a more detailed understanding of the metabolic pathways in living cells. The structure of these complexes, the location and orientation of the aromatic polycyclic residues attached to nucleic acids are studied by a combination of fluorescence, phosphorescence, triplet flash photolysis, electric linear dichroism and optically detected magnetic resonance techniques.
NIH ExPorter
NIH ExPorter