Analysis of Phenanthrene and Benzo[<i>a</i>]pyrene Tetraol Enantiomers in Human Urine: Relevance to the Bay Region Diol Epoxide Hypothesis of Benzo[<i>a</i>]pyrene Carcinogenesis and to Biomarker Studies

Hecht, Stephen S.; Carmella, Steven G.; Villalta, Peter W.; Hochalter, J. Bradley

doi:10.1021/tx9004538

Cited by 70 publications

(60 citation statements)

References 50 publications

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“…With 10 mL of urine samples, the LODs varied from 20 pg·mL − 1 (B[a]P-tetrol) to 110 pg·mL −1 3-OH-Pyr). These values compare favorably to LODs previously reported via chromatographic methods [18][19][20][21][22][23][24][25][26][27][28].…”

Section: Resultssupporting

confidence: 83%

Room temperature fluorescence spectroscopy of benzo[a]pyrene metabolites on octadecyl extraction membranes

Alfarhani

Al-Tameemi

Schenone

et al. 2016

Microchemical Journal

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a b s t r a c tBenzo[a]pyrene (B[a]P) is a prototypic carcinogenic polycyclic aromatic hydrocarbon (PAH), which requires metabolic activation to produce its detrimental effects. Measurement of B[a]P metabolites in human urine could provide a direct way to assess individual differences in susceptibility to PAH-related cancer. This article focuses on the development of screening methodology for the routine analysis of B[a]P metabolites in urine samples. It explores the solid-surface room-temperature fluorescence (RTF) properties of 3-hydroxybenzo[a]pyrene, benzo[a]pyrene-trans-9,10-dihydrodiol, benzo[a]pyrene-r-7,t-8,c-9-tetrahydrotriol and benzo[a]pyrene-r-7,t-8,c-9,c-10-tetrahydrotetrol previously extracted from urine samples with octadecyl-silica membranes. Relative standard deviations varying from 2.1% (benzo[a]pyrene-r-7,t-8,c-9-tetrahydrotriol) to 8.6% (3-hydroxy-benzo[a]pyrene) are obtained with the aid of fiber optic probe that eliminates the need for manual optimization of signal intensities. Analytical recoveries from human urine samples varied from 87.5 ± 3.1% (3-hydroxy-benzo[a]pyrene) to 99.8 ± 2.5% (benzo[a]pyrene-r-7,t-8,c-9,c-10-tetrahydrotetrol). The excellent analytical figures of merit and the simplicity of the experimental procedure demonstrate the potential of this approach for screening biomarkers of PAH exposure in numerous urine samples.

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Section: Resultssupporting

confidence: 83%

Room temperature fluorescence spectroscopy of benzo[a]pyrene metabolites on octadecyl extraction membranes

Alfarhani

Al-Tameemi

Schenone

et al. 2016

Microchemical Journal

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“…In many cases, however, AHR activation and metabolism by CYP enzymes increases PAH reactivity and toxicity, which is consequential to the PAH, route of exposure, and exposure concentration (Nebert et al , 2004; Shi et al , 2010; Kerley-Hamilton et al , 2012). The low molecular weight PAHs (2–3 rings) are generally poor AHR ligands and less potent carcinogens, but are often detected at higher levels in environmental samples and human urine than their higher molecular weight counterparts (Durant et al , 1996; Naumova et al , 2002; Ciganek et al , 2004; Hecht et al , 2010). …”

Section: Introductionmentioning

confidence: 99%

Structurally distinct polycyclic aromatic hydrocarbons induce differential transcriptional responses in developing zebrafish

Goodale

Tilton

Corvi

et al. 2013

Toxicology and Applied Pharmacology

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Polycyclic aromatic hydrocarbons (PAHs) are ubiquitous in the environment as components of fossil fuels and by-products of combustion. These multi-ring chemicals differentially activate the Aryl Hydrocarbon Receptor (AHR) in a structurally dependent manner, and induce toxicity via both AHR-dependent and-independent mechanisms. PAH exposure is known to induce developmental malformations in zebrafish embryos, and recent studies have shown cardiac toxicity induced by compounds with low AHR affinity. Unraveling the potentially diverse molecular mechanisms of PAH toxicity is essential for understanding the hazard posed by complex PAH mixtures present in the environment. We analyzed transcriptional responses to PAH exposure in zebrafish embryos exposed to benz(a)anthracene (BAA), dibenzothiophene (DBT) and pyrene (PYR) at concentrations that induced developmental malformations by 120 hours post-fertilization (hpf). Whole genome microarray analysis of mRNA expression at 24 and 48 hpf identified genes that were differentially regulated over time and in response to the three PAH structures. PAH body burdens were analyzed at both time points using GC-MS, and demonstrated differences in PAH uptake into the embryos. This was important for discerning dose-related differences from those that represented unique molecular mechanisms. While BAA misregulated the least number of transcripts, it caused strong induction of cyp1a and other genes known to be downstream of the AHR, which were not induced by the other two PAHs. Analysis of functional roles of misregulated genes and their predicted regulatory transcription factors also distinguished the BAA response from regulatory networks disrupted by DBT and PYR exposure. These results indicate that systems approaches can be used to classify the toxicity of PAHs based on the networks perturbed following exposure, and may provide a path for unraveling the toxicity of complex PAH mixtures.

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“…PAHs are a concern because several of its members have been known to cause cancer in humans (Hecht et al, 2010). The U.S. Environmental Protection Agency (EPA) has identified 16 PAHs as priority pollutants because of their suspected carcinogenicity and high toxicity (Agency for Toxic Substances, 1995).…”

Section: Introductionmentioning

confidence: 99%

A highly sensitive monoclonal antibody based biosensor for quantifying 3–5 ring polycyclic aromatic hydrocarbons (PAHs) in aqueous environmental samples

Kaattari

Vogelbein

et al. 2016

Sensing and Bio-Sensing Research

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Immunoassays based on monoclonal antibodies (mAbs) are highly sensitive for the detection of polycyclic aromatic hydrocarbons (PAHs) and can be employed to determine concentrations in near real-time. A sensitive generic mAb against PAHs, named as 2G8, was developed by a three-step screening procedure. It exhibited nearly uniformly high sensitivity against 3-ring to 5-ring unsubstituted PAHs and their common environmental methylated PAHs, with IC50 values between 1.68–31 μg/L (ppb). 2G8 has been successfully applied on the KinExA Inline Biosensor system for quantifying 3-5 ring PAHs in aqueous environmental samples. PAHs were detected at a concentration as low as 0.2 μg/L. Furthermore, the analyses only required 10 min for each sample. To evaluate the accuracy of the 2G8-based biosensor, the total PAH concentrations in a series of environmental samples analyzed by biosensor and GC-MS were compared. In most cases, the results yielded a good correlation between methods. This indicates that generic antibody 2G8 based biosensor possesses significant promise for a low cost, rapid method for PAH determination in aqueous samples.

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Analysis of Phenanthrene and Benzo[a]pyrene Tetraol Enantiomers in Human Urine: Relevance to the Bay Region Diol Epoxide Hypothesis of Benzo[a]pyrene Carcinogenesis and to Biomarker Studies

Cited by 70 publications

References 50 publications

Room temperature fluorescence spectroscopy of benzo[a]pyrene metabolites on octadecyl extraction membranes

Room temperature fluorescence spectroscopy of benzo[a]pyrene metabolites on octadecyl extraction membranes

Structurally distinct polycyclic aromatic hydrocarbons induce differential transcriptional responses in developing zebrafish

A highly sensitive monoclonal antibody based biosensor for quantifying 3–5 ring polycyclic aromatic hydrocarbons (PAHs) in aqueous environmental samples

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