The world's first wiki where authorship really matters (Nature Genetics, 2008). Due credit and reputation for authors. Imagine a global collaborative knowledge base for original thoughts. Search thousands of articles and collaborate with scientists around the globe.

wikigene or wiki gene protein drug chemical gene disease author authorship tracking collaborative publishing evolutionary knowledge reputation system wiki2.0 global collaboration genes proteins drugs chemicals diseases compound
Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

Synthesis and mutagenicity of 1-nitro-6-nitrosopyrene and 1-nitro-8-nitrosopyrene, potential intermediates in the metabolic activation of 1,6- and 1,8-dinitropyrene.

1,6-Dinitropyrene and 1,8-dinitropyrene are environmental contaminants which are mutagenic in bacteria and cultured mammalian cells. Since nitroreduction, and possibly O-acetylation, have been implicated in the metabolic activation of these compounds, the reduced intermediates, 1-nitro-6-nitrosopyrene and 1-nitro-8-nitrosopyrene, were synthesized and their mutagenicity examined in Salmonella typhimurium and Chinese hamster ovary (CHO) cells. Nitration of 1-acetylaminopyrene yielded a mixture of 1-acetylamino-6-nitropyrene and 1-acetylamino-8-nitropyrene, which was separated by flash chromatography. Following deacetylation, the amino-nitropyrenes were oxidized to the desired nitronitrosopyrenes with m-chloroperoxybenzoic acid. Both nitronitrosopyrenes showed similar levels of mutagenicity in S. typhimurium strain TA98 and a nitroreductase-deficient analogue, TA98NR, but much lower activity in the esterificase-deficient strain, TA98/1,8-DNP6, which suggested that reduced metabolites require further activation by O-acetylation. In contrast, the analogous compound, 1-nitrosopyrene, was equally mutagenic in all three strains while its parent compound, 1-nitropyrene, demonstrated a much reduced mutagenicity in strain TA98NR. In CHO cells, 1-nitropyrene was not mutagenic and the dinitropyrenes were only weakly active, while all three nitrosopyrene derivatives were highly mutagenic. These data support the hypothesis that nitrated pyrenes are metabolized to mutagens through nitroreduction. In Salmonella the limiting step in the metabolic activation of 1-nitropyrene appears to be the initial reduction to 1-nitrosopyrene, while with the dinitropyrenes subsequent esterification of the reduced intermediates seems critical. With CHO cells, the initial reduction to nitroso derivatives is the limiting step for all nitropyrenes, and esterification does not appear to occur in the activation sequence.[1]


WikiGenes - Universities