The mutagenicity of benzo[alpyrene and 15 of its derivatives, which included phenols, the benzo[a]pyrene4,5-epoxide (the K-region epoxide), dihydrodiols, two isomeric 7,8-diol-9,10-epoxides, a 6-methyl derivative, and a 6-hydroxymethyl derivative, were tested with Chinese hamster V79 cells in order to identify the (3,(8)(9)(10)(11)(12)(13)(14).Mutagenesis by these compounds was tested in Chinese hamster V79 cells, and mutation was characterized by resistance to ouabain (15)

Inflammatory cells infiltrate the liver in response to microbial infection or hepatic injury. To assess the potential role hepatocytes may play in initiating or amplifying the acute inflammatory response in the liver, we used three human hepatocyte cell lines and primary human hepatocyte cultures to characterize the repertoire of cytokines that can be expressed and regulated in hepatocytes in response to agonist stimulation or bacterial infection. As reported herein, a proinflammatory cytokine gene program that includes C-X-C and C-C chemokines [interleukin-8(IL-8), growth related (GRO)-alpha, GRO-beta, GRO-gamma, epithelial neutrophil activating peptide-78 (ENA-78), and RANTES] and the cytokines tumor necrosis factor-alpha (TNF-alpha) and macrophage colony stimulating factor was upregulated in human hepatocytes after stimulation with IL-1 alpha or TNF-alpha or bacterial invasion. In contrast, expression of hematopoietic/ lymphoid growth factors by the same cells was either down-regulated (erythropoietin and stem cell factor) or unchanged (IL-7 and IL-15) in response to the identical stimuli. Hepatocytes did not express cytokines that often are associated with the regulation of antigen-specific immune responses (IL-2, IL-4, IL-5, IL-10, IL-12p40, IL-13, and interferon-gamma) or genes for several other proinflammatory cytokines [IL-1 alpha, IL-6, monocyte chemotactic protein-1 (MCP-1), and MCP-3] or hematopoietic growth factors (granulocyte colony stimulating factor, granulocyte macrophage colony stimulating factor, IL-3, and IL-11). Together, these studies suggest that hepatocytes can both initiate and amplify acute inflammatory responses in the liver through the regulated expression and secretion of a specific array of proinflammatory cytokines.

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The fungus Cunninghamella elegans oxidized anthracene and phenanthrene to form predominately transdihydrodiols. The metabolites were isolated by reversed-phase high-pressure liquid chromatography for structural and conformational analyses. Comparison of the circular dichroism spectrum of the fungal trans-1,2-dihydroxy-1,2-dihydroanthracene to that formed by rat liver microsomes indicated that the major enantiomer of the trans-1,2-dihydroxy-1,2-dihydroanthracene formed by C. elegans had an S,S absolute stereochemistry, which is opposite to the predominately 1R,2R dihydrodiol formed by rat liver microsomes. C. elegans oxidized phenanthrene primarily in the 1,2-positions to form trans-1,2-dihydroxy-1,2-dihydrophenanthrene. In addition, a minor amount of trans-3,4-dihydroxy-3,4-dihydrophenanthrene was detected. Metabolism at the K-region (9,10-positions) of phenanthrene was not detected. Comparison of the circular dichroism spectra of the phenanthrene trans-1,2and trans-3,4-dihydrodiols formed by C. elegans to those formed by mammalian enzymes indicated that each of the dihydrodiols formed by C. elegans had an S,S absolute configuration. The results indicate that there are differences in both the regio-and stereoselective metabolism of anthracene and phenanthrene between the fungus C. elegans and rat liver microsomes.

Benzofajpyrene is stereospecifically converted in two enzymatic steps by rat liver microsomal mixed-function oxidases and epoxide hydratase to the (-) enantiomers of the trans-4,5-, /rani-7,8-, and /rans-9,10-diols. The initial mixed-function epoxidation at the 4,5, 7,8, and 9,10 positions occurs at one side of the planar benzo[a]pyrene molecule to form epoxide intermediates, and this is followed by a substrate-stereoselective and a product-stereospecific hydration of the epoxide intermediates by epoxide hydratase to the (-)-rrans-diols. The identification of the diols as optically pure (-)-trans enantiomers was accomplished by high-pressure liquid chromatographic separation of the cis and trans isomers, and of the di-(-)-menthoxyacetates of the (+)and (-)-trans enantiomers. Incubation of benzofajpyrene with rat liver Benzofajpyrene (BP)* 1 is the most commonly studied polycyclic aromatic hydrocarbon of the environment and exerts several biological effects (Particulate Polycyclic Organic Matter, National Academy of Sciences, 1972). The biological activities included toxicity, mutagenicity, tumorigenicity, and covalent binding to DNA (