Characteristics of Noncovalent and Covalent Interactions of (+) and (-) Anti-Benzo(a)Pyrene Diol Epoxide Stereoisomers of Different Biological Activities with DNA

摘要

The (+) and (-) enantiometers of anti-7,8-diol-9,10-epoxy-7,8,9,10-tetrahydrobenzo (a) pyrene (BPDE) are characterized by striking differences in their tumorigenic and mutagenic activities. The covalent binding of these isomers leads to DNA adducts with different distributions of conformations. The adducts derived from (+)-BPDE cause significant unwinding of supercoiled DNA, while those derived from (-)-BPDE do not. The conformations of these covalent lesions are different from those of classical intercalation complexes and include external binding modes and adducts which exhibit some though not all characteristics of intercalative binding.