Cyclopenta[c]phenanthrenes – Chemistry and biological activity

• Published in: Chemico-biological interactions 2013-06, Vol.204 (1), p.58-65
• Main Authors: Brzuzan, Paweł, Góra, Maciej, Łuczyński, Michał K., Woźny, Maciej
• Format: Article
• Language: English
• Subjects: adverse effects; agonists; Ames test; Animals; benzo(a)pyrene; correlation; CP[c]Ph; Cyclization; Cytochrome P-450 Enzyme System - metabolism; environmental hazards; erythrocytes; Estrogen Receptor alpha - metabolism; exposure pathways; fish; Gene expression; gene expression regulation; genes; Genes, p53 - genetics; Genotoxicity; kidneys; liver; Liver - drug effects; messenger RNA; Molecular Structure; Mutagenicity; Oncorhynchus mykiss; PAHs; phenanthrene; Phenanthrenes - chemical synthesis; Phenanthrenes - chemistry; Phenanthrenes - toxicity; polycyclic aromatic hydrocarbons; risk assessment process; skeleton; Synthesis; Transcription, Genetic - drug effects; Water Pollutants, Chemical - toxicity
• ISSN: 0009-2797; 1872-7786
• DOI: 10.1016/j.cbi.2013.04.009

•Cyclopenta-fused PAHs have been detected in the environment.•Few synthetic pathways are used to construct cyclopenta[c]phenanthrene (CP[c]Ph).•CP[c]Ph modulates gene expression of various molecular pathways in fish tissues.•Bioactivated CP[c]Phs are mutagenic and genotoxic. Despite cyclopenta-fused polycyclic aromatic hydrocarbons (CP-PAHs) having been detected in the environment, the ability of these compounds to induce cellular and tissue responses remains poorly characterized. In this review, we look at the chemistry and biological activity of the cyclopenta[c]phenanthrenes (CP[c]Phs) as potential chemicals of concern in the process of risk assessment. The first part of the review deals with the environmental occurrence and chemistry of CP-PAHs, focusing on available methods of CP[c]Ph chemical synthesis. The most interesting structural feature of the CP[c]Ph is the presence of a pseudo fjord-region constructed by the cyclopentane ring. This compound can be treated either as a structurally similar one to B[c]Ph, or as a phenanthrene skeleton with an electrodonating alkyl substituent in the bay-region of the molecule. The second thread, providing available data on the adverse effects of CP[c]Ph compounds on cells and tissues of living organisms, mainly fish, improves our understanding of these possible environmental hazards. The data show that CP[c]Ph is less potent at inducing CYP1A gene expression in rainbow trout than benzo[a]pyrene (B[a]P), a well-known Ah-receptor agonist. Interestingly, the CP[c]Ph dependent up-regulation of CYP1A mRNA is positively correlated with the incidences of clastogenic changes in rainbow trout erythrocytes. CP[c]Ph has, comparably to B[a]P, a potential to repress expression of tumor suppressor p53, in the head kidney of rainbow trout. Furthermore, estrogen responsive genes in fish liver, ERα and VTG, are not induced by CP[c]Ph, suggesting that the compound has no endocrine disrupting potential. However, some CP[c]Phs show mutagenic activity when investigated in the Ames test, and exhibit genotoxic properties in in vitro micronucleus assay. The above characteristics suggest that CP-PAHs are chemicals of concern for which potential pathways of exposure should be further identified.