Metabolic Activation Pathways of Cyclopenta-Fused PAH (Polycyclic Aromatic Hydrocarbons) and Their Relationship to Genetic and Carcinogenic Activity

摘要

Cyclopenta-fused PAH are a novel class of environmental PAH of which the most well known example is cyclopenta(cd)pyrene. The fusion of an unsaturated cyclopenta-ring on a PAH in general, markedly enhances its activity as a gene mutagen in bacteria and cultured mammalian cells, a cell transforming agent in rodent cells and a mouse skin tumor initiator. A series of four cyclopenta-fused isomers of benz(a)anthracene and the cyclopenta-fused isomers of anthracene and phenanthrene were studied with respect to the major rat liver microsomal metabolites, their activity as gene mutagens in Salmonella typhimurium and Chinese hamster V79 cells and their ability to morphologically transform C3H10T1/2CL8 mouse embryo fibroblasts. For all six isomers, the dihydrodiol arising from oxidation and hydration at the cyclopenta-ring was a major pathway in Aroclor-1254 induced rat liver microsomes. All six isomers were active in mutating Salmonella typhimurium and the four benz(a)anthracene isomers active in mutating V79 cells at the HGPRT locus.