cyclopenta(cd)pyrene-3-4-oxide and cyclopenta(c-d)pyrene

Cyclopenta(cd)pyrene (CPP), a polycyclic aromatic hydrocarbon without a bay region, is a potent bacterial mutagen. The experiments reported in this paper demonstrate that the major CPP metabolite generated by liver microsomes prepared from either phenobarbital or 3-methylcholanthrene pretreated rats is the optically active trans-3,4-dihydroxy-3,4-dihydrocyclopenta(cd)pyrene. Other experiments indicate that formation of the trans-3,4-dihydrodiol of CPP probably proceeds via enzymatic hydrolysis of 3,4-epoxycyclopenta(cd)pyrene by opening of the O--C(3) bond. (a) The racemic 3,4-epoxycyclopenta(cd)pyrene has been synthesized via the bromohydrin of CPP and shown to hydrolyze primarily to 3,4-dihydrocyclopenta(cd)pyrene-4-one and to mixtures of the trans- and cis-3,4-dihydrodiols. Detection of 3,4-dihydrocyclopenta(cd)pyrene-4-one as the major acid catalyzed rearrangement product indicates the opening of the epoxide at the C(3) position to yield a carbonium ion followed by an NIH shift. (b) The synthetic epoxide is potently mutagenic to bacteria with a similar spectrum of mutagenicity against Salmonella typhimurium strains carrying base-pair substitution or frameshift mutations as was seen with CPP in the presence of liver enzymes. These results indicate that 3,4-epoxycyclopenta(cd)pyrene is the major microsomal and mutagenic metabolite of CPP.

Topics: Animals; Cyclopentanes; Microsomes, Liver; Mutagenicity Tests; Mutagens; Oxidation-Reduction; Pyrenes; Rats; Salmonella typhimurium; Structure-Activity Relationship

Cyclopenta(cd)pyrene, a constituent of environmental emissions, has been found to mutate and transform mammalian cells in culture. Cyclopenta(cd)pyrene 3,4-oxide, a presumed metabolite, was found to be a direct-acting mutagen and to transform mammalian cells. These results suggest that cyclopenta(cd)pyrene 3,4-oxide may be an ultimate mutagenic form of the parent hydrocarbon.

Topics: Animals; Cell Line; Cell Transformation, Neoplastic; Cyclopentanes; Mice; Mutagens; Pyrenes; Structure-Activity Relationship