Formation of radical cations in a model for the metabolism of aromatic hydrocarbons

Lehner, Andreas F.; Horn, Jamie; Flesher, James W.

doi:10.1016/j.bbrc.2004.08.017

Cited by 21 publications

(16 citation statements)

References 19 publications

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“…The values of anodic peak potentials and ionization potentials have been found to be important parameters for the carcinogenic activity of studied compounds [39 -41]. However, this hypothesis is contrary to the very recent observations of Lehner et al performed by gas chromatography-mass spectrometry [42] who concluded that the carcinogenicities of BaP and some other PAHs, with relatively low ionization potentials, are independent of one-electron oxidation to radical cation intermediates. They noted that a great number of noncarcinogenic hydrocarbons are known to have low ionization potentials conversely; some hydrocarbons with relatively high ionization potentials have been shown to be carcinogens.…”

Section: Introductioncontrasting

confidence: 56%

Voltammetry of Benzo[a]pyrene in Aqueous and Nonaqueous Media: Adsorptive Stripping Voltammetric Determination at Pencil Graphite Electrode

2010

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A detailed study of the electrochemical oxidation of Benzo[a]pyrene (BaP) at the glassy carbon and pencil graphite electrodes was carried out in aqueous and nonaqueous media. Using square-wave stripping mode, the compound yielded a well-defined voltammetric response at pencil graphite electrode in acetate buffer, pH 4.8 at þ 1.13 V (vs. Ag/ AgCl) (a preconcentration step being carried out at a fixed potential of þ 0.70 V for 180 s). The process could be used to determine BaP concentrations in the range 0.25 -1.25 mM, with a detection limit of 0.027 mM (6.82 mg L À1). The applicability to assay of spiked human urine samples was also illustrated.

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Section: Introductioncontrasting

confidence: 56%

Voltammetry of Benzo[a]pyrene in Aqueous and Nonaqueous Media: Adsorptive Stripping Voltammetric Determination at Pencil Graphite Electrode

2010

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“…By using the low‐energy collisional activation and tandem mass spectrometry, one can control the amount of energy transferred in to an ion by varying the collision energy (CE) and accordingly the fragmentation rate. The compound specific ERMS curves are therefore exploited by many authors for the characterization of position and stereo isomers and even for conformational analysis …”

Section: Introductionmentioning

confidence: 99%

Identification of position isomers by energy‐resolved mass spectrometry

Menacherry

Laprévôte²,

Nguyen

et al. 2015

J. Mass Spectrom.

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This study reports an energy-resolved mass spectrometric (ERMS) strategy for the characterization of position isomers derived from the reaction of hydroxyl radicals ((●)OH) with diphenhydramine (DPH) that are usually hard to differentiate by other methods. The isomer analogues formed by (●)OH attack on the side chain of DPH are identified with the help of a specific fragment ion peak (m/z 88) in the collision-induced dissociation (CID) spectrum of the protonated molecule. In the negative ion mode, the breakdown curves of the deprotonated molecules show an order of stability (supported by density functional theory (DFT) calculations) ortho > meta > para of the positional isomers formed by the hydroxylation of the aromatic ring. The gas phase stability of the deprotonated molecules [M - H](-) towards the benzylic cleavage depends mainly on the formation of intramolecular hydrogen bonds and of the mesomeric effect of the phenol hydroxyl. The [M - H](-) molecules of ortho and meta isomers result a peak at m/z 183 with notably different intensities because of the presence/absence of an intramolecular hydrogen bonding between the OH group and C9 protons. The ERMS approach discussed in this report might be an effective replacement for the conventional methods that requires very costly and time-consuming separation/purification methods along with the use of multi-spectroscopic methods.

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“…One-electron oxidation of PAHs was investigated chemically by treating PAH with iodine, and manganese acetate; electrochemically, and by the use of either horseradish peroxidase plus H 2 O 2 or by rat liver microsomes plus CuOOH. Recently a more efficient chemical method 44 reported a conversion of 50% B[ a ]P into its radical cation. However, these studies did not find any correlation between the ionization potentials of different PAH and their mutagenic potency, leading the authors to conclude that radical cation formation does not correlate with mutagenesis.…”

Section: Discussionmentioning

confidence: 99%

p53 Mutagenesis by Benzo[a]pyrene Derived Radical Cations

Sen

Bhojnagarwala

Francey

et al. 2012

Chem. Res. Toxicol.

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Benzo[a]pyrene (B[a]P), a major human carcinogen in combustion products such as cigarette smoke and diesel exhaust, is metabolically activated into DNA-reactive metabolites via three different enzymatic pathways. The pathways are the anti-(+)-benzo[a]pyrene 7,8-diol 9, 10-epoxide pathway (P450/ epoxide hydrolase catalyzed) (B[a]PDE), the benzo[a]pyrene o-quinone pathway (aldo ketose reductase (AKR) catalyzed) and the B[a]P radical cation pathway (P450 peroxidase catalyzed). We used a yeast p53 mutagenesis system to assess mutagenesis by B[a]P radical cations. Because radical cations are short-lived, they were generated in situ by reacting B[a]P with cumene hydroperoxide (CuOOH) and horse radish peroxidase (HRP) and then monitoring the generation of the more stable downstream products, B[a]P-1,6-dione and B[a]P-3,6-dione. Based on the B[a]P-1,6 and 3,6-dione formation, approximately 4µM of radical cation was generated. In the mutagenesis assays, the radical cations produced in situ showed a dose-dependent increase in mutagenicity from 0.25 µM to 10 µM B[a]P with no significant increase seen with further escalation to 50 µM B[a]P. However, mutagenesis was 200-fold less than with the AKR pathway derived B[a]P, 7–8 dione. Mutant p53 plasmids, which yield red colonies, were recovered from the yeast to study the pattern and spectrum of mutations. The mutation pattern observed was G to T (31%) > G to C (29%) > G to A (14%). The frequency of codons mutated by the B[a]P radical cations was essentially random and not enriched at known cancer hotspots. The quinone products of radical cations, B[a]P-1,6-dione and B[a]P-3,6-dione were more mutagenic than the radical cation reactions, but still less mutagenic than AKR derived B[a]P-7,8-dione. We conclude that B[a]P radical cations and their quinone products are weakly mutagenic in this yeast-based system compared to redox cycling PAH o-quinones.

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Formation of radical cations in a model for the metabolism of aromatic hydrocarbons

Cited by 21 publications

References 19 publications

Voltammetry of Benzo[a]pyrene in Aqueous and Nonaqueous Media: Adsorptive Stripping Voltammetric Determination at Pencil Graphite Electrode

Voltammetry of Benzo[a]pyrene in Aqueous and Nonaqueous Media: Adsorptive Stripping Voltammetric Determination at Pencil Graphite Electrode

Identification of position isomers by energy‐resolved mass spectrometry

p53 Mutagenesis by Benzo[a]pyrene Derived Radical Cations

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