Is intercalation a critical factor in the covalent binding of mutagenic and tumorigenic polycyclic aromatic diol epoxides to DNA

摘要: The tumorigenic and mutagenic effects induced by polycyclic aromatic diol epoxides are widely believed to involve the covalent binding of these electrophilic metabolites hydrocarbons DNA. Here relationships between formation non-covalent intercalation complexes with DNA, DNA-catalyzed reaction rates, tetraols (which constitutes a detoxification pathway) level examined critically within context available experimental results. When rates epoxide molecules at DNA sites dominate over those in external aqueous solution, is independent intercalative (association constant K, M-1) which precedes reaction. However, under conditions does not catalyze or enhance rate (e.g. high salt concentrations), when there efficient competitive pathways solution predicted be directly proportional K. Since latter expected prevail cellular environment, ability given derivative form prior should an important factor determining biological activities compounds. suitable for testing complex vitro described.