Identification of benzene oxide as a product of benzene metabolism by mouse, rat, and human liver microsomes

Lovern, Mark; Turner, M. J.; Meyer, Martine; Kedderis, Gregory L.; Bechtold, William E.; Schlosser, Paul M.

doi:10.1093/carcin/18.9.1695

Cited by 55 publications

(28 citation statements)

References 19 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Incubations of either [U-14 C]benzene or [U-14 C]phenol with mouse or rat liver microsomes (1 mg/ml final concentration) were performed as described previously (18,19). Final concentrations for each substrate species combination were as follows (mean Ϯ SD): 14.3 Ϯ 2.2 µM (benzene, mouse), 13.8 Ϯ 1.8 µM (benzene, rat), 304 Ϯ 0.7 µM (phenol, mouse) and 303 Ϯ 1 µM (phenol, rat).…”

Section: Incubation Proceduresmentioning

confidence: 99%

“…Analysis of ethylacetate extracts was by HPLC followed by LSS, as described previously (18,19). Aqueous samples were separated on a 4.6ϫ250 mm C-18, 5-µm reverse phase HPLC column with a 0.5 µm inlet filter (Altech, Deerfield, IL).…”

Section: Chemical Analysismentioning

confidence: 99%

“…At present, trans-trans-muconaldehyde, an open ring metabolite, as well as quinones and radicals formed from the oxidation of hydroquinone are among the suspect agents (17). Recently, it has been reported that GC/MS analysis of samples from microsomal incubations of 1 mM benzene revealed the presence of benzene oxide, the initial oxidative metabolite of benzene (18). HPLC analysis of an authentic standard for benzene oxide revealed that its elution time matched exactly that of an unknown metabolite reported by Seaton et al (19).…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Use of a mathematical model of rodent in vitro benzene metabolism to predict human in vitro metabolism data

1999

View full text Add to dashboard Cite

Benzene, a ubiquitous environmental pollutant, is known to cause leukemia and aplastic anemia in humans and hematotoxicity and myelotoxicity in rodents. Toxicity is thought to be exerted through oxidative metabolites formed in the liver, primarily via pathways mediated by cytochrome P450 2E1 (CYP2E1). Phenol, hydroquinone and transtrans-muconaldehyde have all been hypothesized to be involved in benzene-induced toxicity. Recent reports indicate that benzene oxide is produced in vitro and in vivo and may be sufficiently stable to reach the bone marrow. Benzene and phenol were also incubated with mouse microsomes in the presence of trans-dichloroethylene, a CYP2E1 inhibitor, and benzene was incubated with trichloropropene oxide, an epoxide hydrolase inhibitor. These experiments did not indicate significant contributions of enzymes other than CYP2E1. Mathematical model parameters were fitted to rodent data and the model was validated by predicting human data. Model simulations predicted the qualitative behavior of three human time course data sets and explained up to 81% of the total variation in data from incubations of benzene for 16 min with microsomes from nine human individuals. While model predictions did deviate systematically from the data for benzene oxide and trihydroxybenzene, overall model performance in predicting the human data was good. The model should be useful in quantifying human risk due to benzene exposure and explicitly accounts for interindividual variation in CYP2E1 activity.

show abstract

Section: Incubation Proceduresmentioning

confidence: 99%

Section: Chemical Analysismentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Use of a mathematical model of rodent in vitro benzene metabolism to predict human in vitro metabolism data

1999

View full text Add to dashboard Cite

show abstract

“…Benzene is oxidized in the liver by cytochrome P4502E1 to form benzene oxide (7)(8)(9), which gives rise to phenol, catechol, hydroquinone, 1,2,4-benzenetriol, and ring-opened metabolites such as trans-trans-muconic acid (10,11). It is the reactive metabolites of benzene that are responsible for myelotoxicity.…”

mentioning

confidence: 99%

Attomole Detection of in Vivo Protein Targets of Benzene in Mice

Williams

Carver

Miranda

et al. 2002

Molecular & Cellular Proteomics

View full text Add to dashboard Cite

Modified proteins were detected in liver and bone marrow of mice following treatment with [ 14 C]benzene. Stained sections were excised from one-dimensional and twodimensional gels and converted to graphite to enable 14 C/ 13 C ratios to be measured by accelerator mass spectrometry. Protein adducts of benzene or its metabolites were indicated by elevated levels of 14 C. A number of proteins were identified by in-gel proteolysis and conventional mass spectrometric methods with the low molecular weight proteins identified including hemoglobin and several histones. The incorporation of 14 C was largely proportional to the density of gel staining, giving little evidence that these proteins were specific targets for selective labeling. This was also true for individual histones subfractionated with Triton-acid-urea gels. A representative histone, H4, was isolated and digested with endopeptidase Asp-N, and the resulting peptides were separated by high performance liquid chromatography. 14 C levels in collected fractions were determined, and the peptides were identified by conventional mass spectrometry. The modifications were distributed throughout the protein, and no particular amino acids or groups of amino acids were identified as selective targets. Thus chemical attack by one or more benzene metabolites upon histones was identified and confirmed, but the resulting modifications appeared to be largely nonspecific. This implies high reactivity toward proteins, enabling such attack to occur at multiple sites within multiple targets.

show abstract

“…They take part in photochemical reactions and are major sources of radicals which can oxidise NO to NO 2 : the precursor of ozone (Finlayson-Pitts and Pitts [1]; Reis et al [2]). Exposure to benzene has the potential for adverse health effects as it is genotoxic carcinogen (Snyder and Kalf [3]; Zhang et al [4]; Lovern et al [5]). …”

Section: Introductionmentioning

confidence: 99%

Benzene, toluene and xylene measurements in the vicinity of petrol stations (Toulouse – France)

Simon¹,

Borownjack²,

Touya³

2006

WIT Transactions on the Built Environment, Vol 89

View full text Add to dashboard Cite

The monitoring of air quality on the urban agglomerations is a priority today and, within this framework, the benzene, toluene and xylene (BTX) concentrations are regularly measured. One of their principal atmospheric sources are the petrol stations: indeed, at the time of the filling of the fuel storage tanks or the vehicle tanks, there is vapor release of hydrocarbons, and more particularly of BTX which remains in the atmosphere. In order to study the impact of this source of emission on its vicinity, we choose to measure the concentrations in BTX around a petrol station using passive dosimeters of Radiello type in various points (above the pumps and in the district where the station is).Dosimeters were installed from January 10 to January 30, 2002. The average atmospheric concentrations of benzene and BTX close to the pumps reached 28 and 293 µg.m -3 respectively whereas they are about 8 and 80 µg.m -3 at the roadside. The use of a recovery device for VOC vapours should partially improve the air quality in the district.

show abstract

Identification of benzene oxide as a product of benzene metabolism by mouse, rat, and human liver microsomes

Cited by 55 publications

References 19 publications

Use of a mathematical model of rodent in vitro benzene metabolism to predict human in vitro metabolism data

Use of a mathematical model of rodent in vitro benzene metabolism to predict human in vitro metabolism data

Attomole Detection of in Vivo Protein Targets of Benzene in Mice

Benzene, toluene and xylene measurements in the vicinity of petrol stations (Toulouse – France)

Contact Info

Product

Resources

About