Search results for "biotransformation"
showing 10 items of 183 documents
Direct Analysis of Phase I Metabolites, Phenol Sulfates, Glucuronides and Glutathione Conjugates of Benzo[a]pyrene in Freshly Isolated, Hypothermical…
1996
Abstract The complex biotransformation of benzo[a]pyrene (BaP), the prototype of the class of carcinogenic polycyclic aromatic hydrocarbons, can be used as a tool to characterize the capacity of in vitro systems for the biotransformation of xenobiotics. In order to account for the ability of liver parenchymal cells to metabolize BaP, a method was developed for the isolation, separation and quantitation of its phase I metabolites, e.g. tetrahydrotetraols, trans-dihydrodiols, quinones and phenols, as well as its phase II metabolites, e.g. sulfates, glucuronides and glutathione conjugates, employing a combination of extractive and chromatographic steps. Upon incubation of BaP with freshly isol…
Detection of Reactive Quinones in the Metabolism of Polycyclic Aromatic Hydrocarbons by the Formation of their Glutathione Conjugates
1996
Abstract The biotransformation of polycyclic aromatic hydrocarbons to quinones by rat liver microsomes was investigated. The employment of an electrochemical detector allowed the specific detection of quinones separated by reverse phase HPLC with higher sensitivity as compared to UV detection. Microsomal incubations of benzo[a]pyrene (BP) resulted in the formation of 1,6-, 3,6- and 6,12-quinones, of naphthalene in the detection of naphthalene-1,4-quinone, whereas ortho-quinones could only be detected in trace amounts. Additional protein binding studies showed that only 9–22% of synthetic ortho-quinones could be recovered from microsomal incubations. In order to scavenge possible reactive qu…
Genotoxicity characteristics of reverse diol-epoxides of chrysene.
2017
Trans-3,4-dihydroxy-3,4-dihydrochrysene (chrysene-3,4-diol), a major metabolite of chrysene, is further metabolized by rat liver enzymes to products which effectively revert the his- Salmonella typhimurium strain TA98 to histidine prototrophy, but are only weakly mutagenic in strain TA100 and in Chinese hamster V79 cells (acquisition of resistance to 6-thioguanine). The liver enzyme mediated mutagenicity of chrysene-3,4-diol is substantially enhanced in the presence of 1,1,1-trichloropropene 2,3-oxide, an inhibitor of microsomal epoxide hydrolase. The predominant metabolites of chrysene-3,4-diol, namely the anti- and syn-isomers of its 1,2-oxide (termed reverse diol-epoxides), proved to be …
Covalent DNA adducts formed by benzo[c]chrysene in mouse epidermis and by benzo[c]chrysene fjord-region diol epoxides reacted with DNA and polynucleo…
1997
The metabolic activation in mouse skin of benzo[c]chrysene (B[c]C), a weakly carcinogenic polycyclic aromatic hydrocarbon (PAH) present in coal tar and crude oil, was investigated. Male Parkes mice were treated topically with 0.5 mumol of B[c]C, and DNA was isolated from the treated areas of skin at various times after treatment and analyzed by 32P-postlabeling. Seven adduct spots were detected, at a maximum level of 0.89 fmol of adducts/microgram of DNA. Four B[c]C-DNA adducts persisted in skin for at least 3 weeks. Treatment of mice with 0.5 mumol of the optically pure putative proximate carcinogens (+)- and (-)-trans-benzo[c]chrysene-9,10-dihydrodiols [(+)- and (-)-B[c]C-diols] led to th…
Tumor formation in the neonatal mouse bioassay indicates that the potent carcinogen dibenzo[def,p]chrysene (dibenzo[a,l]pyrene) is activated in vivo …
2004
The hexacyclic aromatic hydrocarbon dibenzo[def,p]chrysene, better known as dibenzo[a,l]pyrene (DBP) in the field of chemical carcinogenesis, is present in the environment as a combustion product of organic matter. This compound is probably the strongest chemical carcinogen ever tested. As ultimate genotoxic metabolites of DBP two electrophilically reactive species are discussed: (i) radical cations generated by one-electron oxidation, and (ii) fjord region dihydrodiol epoxides formed via the trans-11,12-dihydroxy 11,12-dihydro derivative of DBP (11,12-dihydrodiol). In order to delineate the metabolic pathway(s) involved in tumor formation by DBP, newborn Crl:CD-1(ICR)BR mice were intraperi…
Metabolic relation of cyanobacteria to aromatic compounds
2018
Cyanobacteria, also known as blue-green (micro)algae, are able to sustain many types of chemical stress because of metabolic adaptations that allow them to survive and successfully compete in a variety of ecosystems, including polluted ones. As photoautotrophic bacteria, these microorganisms synthesize aromatic amino acids, which are precursors for a large variety of substances that contain aromatic ring(s) and that are naturally formed in the cells of these organisms. Hence, the transformation of aromatic secondary metabolites by cyanobacteria is the result of the possession of a suitable “enzymatic apparatus” to carry out the biosynthesis of these compounds according to cellular requireme…
Biotransformation of caffeine and theophylline in mammalian cell lines genetically engineered for expression of single cytochrome P450 isoforms
1992
Primary steps in the metabolism of caffeine and theophylline are cleavage of methyl groups and/or hydroxylation at position 8, mediated by cytochromes P450. V79 Chinese hamster cells genetically engineered for stable expression of single forms of rat cytochromes P450IA1, P450IA2 and P450IIBI and human P450IA2 and rat liver epithelial cells expressing murine P450IA2 were used to overcome problems arising in the proper allocation of metabolic pathways to specific isoforms by conventional techniques. These cell lines were exposed to caffeine and/or theophylline, and concentrations of metabolites formed in the medium were determined by HPLC. Caffeine was metabolized by human, rat and murine P45…
Applications of stable V79-derived cell lines expressing rat cytochromes P4501A1, 1A2, and 2B1.
1992
1. Chinese hamster V79-derived cell lines, stably expressing cytochromes P4501A1, 1A2, and 2B1 activities, were constructed by genetic engineering in continuation of our work to establish a battery of V79 derived cell lines designed to study the metabolism of xenobiotics. 2. Cell lines XEM1 and XEM2, expressing cytochrome P4501A1, were capable of the O-dealkylation of 7-ethoxycoumarin and the hydroxylation of benzo[a]pyrene. 3. Cell lines XEMd.MZ and XEMd.NH, expressing P4501A2, were shown to hydroxylate 17 beta-estradiol and 2-aminofluorene. 4. Cell line SD1, expressing cytochrome P4502B1, was able to hydroxylate testosterone stereo- and regio-specifically at the 16 alpha and 16 beta posit…
Kinetic experiments on the binding of metyrapone to liver microsomes
1969
Kinetic experiments on the inhibition of oxidative microsomal O- and N-demethylations by metyrapone (2-methyl-1, 2-bis(3-pyridyl)-l-propanone, Su 4885) were carried out using mouse liver microsomes as the enzyme source. The model substrates were p-nitroanisole and N-monomethyl-p-nitroaniline. It was shown that the inhibition is competitive. The K i for metyrapone is 0.42 × 10−4 M and for the reduced metabolite of metyrapone 1.15×10−4 M. Their spectral dissooiation constants as determined from difference spectra have almost the same values. From this it is concluded that the degree of inhibition is correlated to the amount of metyrapone bound to cytochrome P-450. Metyrapone does not seem to …
Biotransformation of methylxanthines in mammalian cell lines genetically engineered for expression of single cytochrome P450 isoforms. Allocation of …
1993
V79 Chinese hamster cells genetically engineered for stable expression of single forms of rat cytochromes P450IA1, P450IA2, P450IIB1, human P450IA2, and rat liver epithelial cells expressing murine P450IA2 were used to allocate metabolic pathways of methylxanthines to specific isoforms and to test the suitability of such cell lines for investigations on drug interactions occurring at the cytochrome expressed. The cell lines were exposed to caffeine and/or theophylline and concentrations of metabolites formed in the medium were determined by HPLC. Caffeine was metabolized by human, rat and murine P450IA2, resulting in the formation of four primary demethylated and hydroxylated metabolites. H…