CHEMISTRY AND BIOLOGY OF CARCINOGEN-DNA ADDUCTS

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.