Metabolic transformation of indeno[1,2,3-cd]pyrene and toxicities of its metabolites.

A porphyrin/peroxynitrite biomimetic system was used to study the metabolism of indeno[1,2,3-cd]pyrene (IND) induced by peroxynitrite. The metabolites were identified using high-performance liquid chromatography coupled with electro-spray ionization tandem mass spectrometry as OH-IND, IND-quinone and 2NO2-IND. By stopping the reaction at different stages, we discovered that IND was first transformed to IND-quinone and 2NO2-IND, which were then transformed to OH-IND. Mutation assays including Ames tests and cell transformation experiments showed enhancement of the mutagenicity after the activation by the peroxynitrite/Fe(III)porphyrin system. The results also showed that 2NO2-IND and IND-quinone played key roles in the mutagenicity of PAHs after metabolic activation.