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)

Acetyl coenzyme A-dependent metabolic activation of N-hydroxy-3,2'-dimethyl-4-aminobiphenyl and several carcinogenic N-hydroxy arylamines in relation to tissue and species differences, other acyl donors, and arylhydroxamic acid-dependent acyltransferases.

The metabolic activation of several carcinogenic N-hydroxy (N-OH)-arylamines by cytosolic S-acetyl coenzyme A (AcCoA)-dependent enzymes was examined in tissues and species susceptible to arylamine carcinogenesis. Comparisons of the AcCoA-dependent activity were also made with known cytosolic arylhydroxamic acid-dependent acyltransferases and with the ability of different acyl donors to mediate the binding of N-OH-arylamines to DNA. With rat hepatic cytosol, AcCoA-dependent DNA binding was demonstrated for several [3H]N-OH-arylamines, in the order: N-OH-3,2'-dimethyl-4-aminobiphenyl (N-OH-DMABP), N-OH-2-aminofluorene (N-OH-AF) greater than N-OH-4-aminobiphenyl greater than N-OH-N'-acetylbenzidine greater than N-OH-2-naphthylamine; N-OH-N-methyl-4-amino-azobenzene was not a substrate. No activity was detected in dog hepatic or bladder cytosol with any of the N-OH-arylamines tested. Using either N-OH-DMABP or N-OH-AF and rat hepatic cytosol, activation to DNA-bound products was also detected with acetoacetyl- and propionyl-CoA but not with folinic acid or six other acyl CoA's. However, p-nitrophenyl acetate which is known to generate acetyl-enzyme intermediates effectively replaced AcCoA. Subcellular fractionation of rat liver showed that the AcCoA-dependent DNA-binding of N-OH-DMABP with cytosol was 5 times greater than that obtained with the microsomal or mitochondrial/nuclear fractions. Furthermore, the cytosolic activity was insensitive to inhibition by the esterase/deacetylase inhibitor, paraoxon; while the activity of the other subcellular fractions was completely inhibited (greater than 95%). AcCoA-dependent activation of N-OH-DMABP was also detected with rat tissue cytosols from intestine, mammary gland and kidney, which like the liver, are targets for arylamine-induced tumorigenesis. Using N-OH-DMABP, AcCoA-dependent DNA-binding activity was also detected in the hepatic cytosols from several species in the order: rabbit greater than hamster greater than rat, human greater than guinea pig greater than mouse. In contrast, the arylhydroxamic acid, N-OH-N-acetyl-DMABP, was not activated to a DNA-binding metabolite by the hepatic cytosolic N,O-acyltransferase of any of these species, thus suggesting that the AcCoA-mediated binding of N-OH-DMABP results from the direct formation of N-acetoxy-DMABP. With N-OH-AF as the substrate, the AcCoA-dependent activation was in the order: rabbit greater than guinea pig, hamster greater than mouse greater than human, rat.(ABSTRACT TRUNCATED AT 400 WORDS)[1]


WikiGenes - Universities