9-Hydroxy-benzo pyrene

Coman et al. [82] used a new modeling of the chromatographic separation process of some polar (hydroxy benzo[a]pyrene derivatives) and nonpolar (benzo[a]pyrene, dibenz[a,/ ]anthracene, and chrysene) polycyclic aromatic compounds in the form of third-degree functions. For the selection of the optimum composition of the benzene-acetone-water mobile phase used in the separation of eight polycyclic aromatic compounds on RP-TLC layers, some computer programs in the GW-BASIC language were written. 

Nineteen outbred male rats were dosed intraperitoneally once with 200 mg/kg benzo[a]pyrene in sunflower oil (Likhachev et al. 1993). Concentrations of benzo[a]pyrene-7,8-diol, a marker metabolite of bioactivation of benzo[a]pyrene. and 3-hydroxy-benzo[a]pyrene, a marker metabolite of deactivation, were measured daily in the urine and feces for 15 days. Levels of these metabolites were correlated with tumor latency. Another group of 10 rats was dosed intraperitoneally once with 15 mg/kg benzo[a]pyrene in sunflower oil and urine was collected for 3 days. Five rats were killed on day 3 and the other 5 were killed on day 8. Liver DNA concentrations of... 

Jongeneelen FJ, Leijdekkers C-M, Bos RP. et al. 1985. Excretion of 3-hydroxy-benzo(o)pyrene and mutagenicity in rat urine after exposure to benzo(a)pyrene. J Appl Toxicol 5 277-282. 

It can also be concluded that dermal absorption occurred as evidenced by the development of skin tumors (Boutwell and Bosch 1958 Lijinsky et al. 1957 Poel and Kammer 1957 Roe et al. 1958) and lung tumors (Roe et al. 1958) in mice following the dermal application of coal tar creosote (see Section 3.2.3.7). Other studies in animals support absorption of coal tar products after dermal application. Coal tar solution (0.05 mL of a 20% solution) was applied to the skin of six neonatal rats (4-6 days of age) and 24 hours later AHH activity was measured in the skin and liver (Bickers and Kappas 1978). There was greater than a 10-fold induction of skin AHH activity (298 13 versus 26.3 19 pmol hydroxy-benzo[a]pyrene/mg protein/hour in controls) and marked increased hepatic AHH activity (16,300 899 versus 750 35 pmol hydroxy-benzo[a]pyrene/mg protein/hour in controls) after topical application of the coal tar solution. 

Glucoside conjugation Spiny lobster 4-Methylumbelliferone 3-Hydroxy- benzo[a]pyrene... 

Values are means + SE for groups of 7. Quantitation was based on the fluorescence of 20ng 3-hydroxy-benzo(a)pyrene and scaled to mg microsomal protein. 

An important improvement of sensitivity was obtained by methylation of the hydroxy groups. As a result even in the bile of fish caught in relatively clean areas (as the Wadden Sea) BaP metabolites could be measured and quantified this is illustrated in Figure 10, showing a LESS spectrum utilizing selective excitation and time-resolved detection. A similar procedure has been applied to determine 3-hydroxy-benzo[rt]pyrene in the urine of coke oven workers. 

Benzo[o]pyrene-rranj-9,10-dihydrodiol 2) Benzolajpy-rene-/r n.s-4,5-dihydrodiol 3) Benzo oJpyrene-(roiM-7.8-di-hydrodiol 4) 9-HydroxybenzolHydroxy-benzo[a]pyrene 8) Benzo[o]pyrene. 

Crassostrea virginica (oysters) benzo[a]pyrene 9,10-dihydroxy-9,10-dihydrobenzo[a]pyrene 4,5 (or 7,8)-dihydroxy-4,5 (or 7,8)-dihydrobenzo[a]pyrene 1,6 (or 3,6)-diketobenzo[a]-pyrene 3-hydroxy-benzo[aj-pyrene... 

After initial metabolism, most of the detoxified portion of PAH compounds are excreted into the bile as metabolites, then subsequently eliminated in the faeces. A smaller proportion is excreted in urine. The two major metabolites of benzo( )pyrene found in urine are 3-hydroxy- and 9-hydroxybenzo(o)pyrene, part of them being conjugated to sulphate or glucuronic acid (Bouchard and Viau, 1997 Ramesh et al., 2001). The process of excretion of PAH compounds into the intestine via the bile, reabsorption, and return to the liver by the portal circulation (enterohepatic recirculation) has been demonstrated to occur for 7,12-dimethylbenzo( )anthracene, benzo(o)pyrene, anthracene and pyrene (Ramesh et al., 2004). Enterohepatic circulation extends the residence time of PAHs in the body and may lead to long half-lives of reactive PAH metabolites. Though enterohepatic recycling of PAHs has... 

Benzo(b)fIuoranthrene la 39, 85 Benzo(k)fluoranthrene la 39, 86 Benzo(ghi)perylene la 39,85 Benzophenone derivatives lb 282 Benzo(a)pyrene la 39,85,103 p-Benzoquinone derivatives la 72 Benzothiazoles lb 237 Benzoyl chloride la 70 Benzoylecgonine lb 32,34,35 3,4-Benzpyrene la 60 Benzthiazide lb 188 Benztriazole, 2-(2-hydroxy-5-methyl-phe-nyl)- la 282... 

A-Hydroxy-4- acetylaminobiphenyl Benzo [a] pyrene diol epoxide Human TK6 lymphoblastoid Custom A-Hydroxy-4- acetylaminobiphenyl 10 xMfor27h Benzo[ajpyrene diol epoxide 10 xM for Ih Gene name, gene symbol, gene bank accession fold change in a table All data available online 116... 

Luo W, Fan W, Xie H, ling L, Ricicki E, Vouros P, et al. Phenotypic anchoring of global gene expression profiles induced by A -hydroxy-4-acetylaminobiphenyl and benzo[a]pyrene diol epoxide reveals correlations between expression profiles and mechanism of toxicity. Chem Res Toxicol 2005 18 619-29. 

The aryl hydroxylase of Saccharomyces cerevisiae that transforms benzo[a]pyrene to the 3- and 9-hydroxy compounds, and the 7,8-dihydrodiol (King et al. 1984). 

In order to gain more detailed information about the physical binding of hydrocarbon metabolites to DNA, studies have also been carried out with model compounds which have many of the steric and electronic properties of carcinogenic epoxides but no reactive epoxide group. The use of nonreactive model compounds permits the clear separation of physical binding interactions from reactive interactions. Benzo[a]pyrene metabolite model compounds which have been examined include 7-hydroxy-7,8,9,10-tetrahydro-BP (4), and cis (4 ) and trans-7,8-dihydroxy-7,8,9,10-tetrahydro-BP (9). 

Hydroxybenzo[a]p3n ene, see Benzo[a]pyrene 9-Hydroxybenzo[a]p3n ene, see Benzo[a]pyrene Hydroxybenzoqninone, see Phenol Hydroxy-p-benzoqninone, see 4-Nitrophenol... 

The first example of syn stereoselective expoxidation of arene dihydrodiols was reported in 1981.11 The trans-dihydrodiols 11 and 12, when treated with a 10-fold excess of MCPBA in tetrahydrofuran (THF) at room temperature, gave stereoselectively the syn-diol epoxides 13 and 14, respectively. This stereoselectivity has been ascribed to the operation of steric control by the axial benzylic hydroxy group the equatorial hydroxy group does not exert such control. The isomeric 9,10-epoxides of 7,8-dihydroxy-7,8-dihydro-benzo[a]pyrene can be prepared by the same method.12... 

Figure 13.7. Glutathione conjugation to reactive metabolites by GSTs. Ultimate carcinogens such as benzo[a]pyrene 7,8-diol 9,10-epoxide and aflatoxin B1 8,9-epoxide are glutathione-conjugated for detoxification by GSTM1, GSTp, and GST A, respectively. Lipid peroxidation product 4-hydroxy-2-nonenal is preferentially detoxified by GSTA.

A similm methodtdqgy was used by Boichardt and coworkers in the synthesis of the phenol (26 Scheme 11). Here, the fact that 4-fluorophenol metallates next to fluorine when the phenol is protected as a TBDMS ether was put to good use for introduction of the hydroxy group, likewise, oxidation of a boron complex was a key step in the synthesis of phenolic dihydrodiols of benzo[a]pyrene, (27) and... 

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