Many chemical substances react with DNA; these reactions occur in a variety of ways. Often modifications in nucleoside structure will subsequently cause replication errors leading to mutations; sometimes these mutations will later progress to malignancies. The overall goal of this Program Project is to develop an understanding on chemical and biological grounds of the relationship between the structures of organic compounds and their ability (1) to modify DNA structure, (2) to induce mutations, and (3) to cause cancer. Effort during this project period will concentrate on the relationship of the structure, i.e., conformation, of DNA covalently modified by carcinogens to the type and frequency of mutations induced by these lesions. These investigations will be carried out with particular emphasis on adducts of polycyclic aromatic hydrocarbons and styrene at exocyclic sites on the nucleosides. Additional studies will be made of ethylene dibromide and malondialdehyde.
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