17573-21-6Relevant articles and documents
Oxidation of Benzo[a]pyrene by Recombinant Human Cytochrome P450 Enzymes
Bauer, Eckhart,Guo, Zuyu,Ueng, Yune-Fang,Bell, L. Chastine,Zeldin, Darryl,Guengerich, F. Peter
, p. 136 - 142 (1995)
The oxidation of benzo[a]pyrene (B[a]P) was examined using reconstituted systems prepared with recombinant human cytochrome P450 (P450) enzymes 1A1, 1A2, 2C8, 2C10, 2E1, and 3A4 and with microsomes prepared from Sacccharomyces cerevisiae expressing recomb
Synthesis of 13C4-labelled oxidized metabolites of the carcinogenic polycyclic aromatic hydrocarbon benzo[a]pyrene
Wu, Anhui,Xu, Daiwang,Lu, Ding,Penning, Trevor M.,Blair, Ian A.,Harvey, Ronald G.
, p. 7217 - 7233 (2012/09/05)
Polycyclic aromatic hydrocarbons (PAHs), such as benzo[a]pyrene (BaP), are ubiquitous environmental contaminants that are implicated in causing lung cancer. BaP is a component of tobacco smoke that is transformed enzymatically to active forms that interact with DNA. We reported previously development of a sensitive stable isotope dilution LC/MS method for analysis of BaP metabolites. We now report efficient syntheses of 13C4-BaP and the complete set of its 13C4-labelled oxidized metabolites needed as internal standards They include the metabolites not involved in carcinogenesis (Group A) and the metabolites implicated in initiation of cancer (Group B). The synthetic approach is novel, entailing use of Pd-catalyzed Suzuki, Sonogashira, and Hartwig cross-coupling reactions combined with PtCl2-catalyzed cyclization of acetylenic compounds. This synthetic method requires fewer steps, employs milder conditions, and product isolation is simpler than conventional methods of PAH synthesis. The syntheses of 13C4-BaP and 13C4-BaP-8-ol each require only four steps, and the 13C-atoms are all introduced in a single step. 13C4-BaP-8-ol serves as the synthetic precursor of all the oxidized metabolites of 13C-BaP implicated in initiation of cancer. The isotopic purities of the synthetic 13C 4-BaP metabolites were estimated to be ≥99.9%.
Synthesis of phenol and quinone metabolites of benzo[a]pyrene, a carcinogenic component of tobacco smoke implicated in lung cancer
Xu, Daiwang,Penning, Trevor M.,Blair, Ian A.,Harvey, Ronald G.
experimental part, p. 597 - 604 (2009/06/20)
Polycyclic aromatic hydrocarbons (PAHs) are widespread environmental pollutants produced in the combustion of organic matter. PAHs are present in automobile exhaust and tobacco smoke, and they have recently been designated as human carcinogens. Current ev
Modulation of cytochrome P4501-mediated bioactivation of benzo[a]pyrene by volatile allyl sulfides in human hepatoma cells.
Chun,Kim,Choi
, p. 2205 - 2212 (2007/10/03)
Allyl sulfides such as diallyl sulfide (DAS), diallyl disulfide (DADS), and diallyl trisulfide (DATS), typical flavor components of Allium vegetables, have been shown to inhibit benzo[a]pyrene (B[a]P)-induced carcinogenesis in animal models. As a possible mechanism of this inhibition, the effect of these volatile substances on cytochrome P450 (CYP)1 (CYP1A1, 1A2 and 1B1)-mediated bioactivation of B[a]P was investigated using a human hepatoma cell model (HepG2). DADS and DATS inhibited the B[a]P-induced ethoxyresorufin O-deethylase (EROD) activity, a marker enzyme for CYP1, by 30-90% and 70-95% at 100-1,000 microM concentration, respectively. The cell viability, an indicator of the capacity to inhibit B[a]P bioactivation, was increased by treatments of 100-1,000 microM DADS and 10-100 microM DATS. Immunoblot results indicated that the B[a]P inducible CYP1A2 protein was suppressed by 100-1,000 microM of DADS and 10-100 microM of DATS, but CYP1A1 and 1B1 were not detectable in any microsomes. Analysis of B[a]P metabolites revealed that the level of 7,8-diol formed was significantly reduced in the DADS and DATS treated microsomes as compared to the control. The level of 9,10-diol and 4,5-diol formed was also lowered by the allyl sulfide treatments. These results suggest that the protective mechanism of allyl sulfides on B[a]P-induced carcinogenesis is possibly related with the modulation of CYP1-mediated bioactivation of B[a]P.
Tetrabutylammonium Hydroxide: A Reagent for the Base-Catalyzed Dehydration of Vicinal Dihydro Diols of Aromatic Hydrocarbons. Implications to Ion-Pair Chromatography
McCourt, David W.,Roller, Peter P.,Gelboin Harry V.
, p. 4157 - 4161 (2007/10/02)
Vicinal dihydro diols of benzopyrene and benzanthracene are dehydrated to their phenolic derivatives by the methanol eluate of reverse-phase (octadecylsilane) columns previously treated with tetrabutylammonium phosphate.Phenols are also produced by treating the dihydro diols with methanolic tetrabutylammonium hydroxide on removal solvent.In most cases the regioselectivity is markedly different from the acid-catalyzed dehydration.The in situ generated tetrabutylammonium phenoxides are converted to the butyl ethers at high temperatures (150 deg C) but not under th e conditions of dehydration (60 deg C).Tetraethylammonium and tetramethylammonium hydroxides also dehydrate dihydro diols, whereas potassium and sodium hydroxides do not.Dehydration does occur by treatment of dihydro diols with potassium hydroxide in the presence of 1,4,7,10,13,16-hexaoxacyclooctadecane (18-crown-6) and with sodium methoxide in the presence of tetrabutylammonium chloride.A mechanism is suggested.
