Chemistry of Muconaldehydes of Possible Relevance to the Toxicology of Benzene

Bleasdale, Christine; Kennedy, Gordon J.; MacGregor, James O.; Nieschalk, Jens; Pearce, Kirsty; Watson, William P.; Golding, Bernard T.

doi:10.2307/3433164

Cited by 9 publications

(11 citation statements)

References 5 publications

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“…The interest in muconaldehyde itself lies in its toxicity. As its precursor benzene, it exhibits carcinogenic activity (bone marrow toxicity) and has also been shown to be cytotoxic and genotoxic to mammalian cells 14a. It can be mentioned in this respect that the metabolic pathways from benzene to muconaldehyde and muconic acid have been the subject of several studies, along with the metabolic pathways of muconaldehyde itself, whose chemistry has been investigated recently 14b…”

Section: Introductionmentioning

confidence: 99%

From Benzene to Muconaldehyde: Theoretical Mechanistic Investigation on Some Tropospheric Oxidation Channels

Ghigo

Tonachini

1999

J. Am. Chem. Soc.

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In the tropospheric oxidation of benzene and methylated benzenes, unsaturated dicarbonyls are commonly detected products. Aldehydes are known to contribute on their own to some aspects of air pollution, and hexa-2,4-dien-1,6-dial (muconaldehyde) in particular is interesting because of its multiform toxicity. This study investigates the likelyhood of some benzene oxidation steps and is especially focused on ring opening and generation of muconaldehyde. With sufficiently high NO x concentration, O abstraction by NO from the cis peroxyl group in the 2-hydroxy-cyclohexadienyl peroxyl radical III can play a role. In fact, it is shown to open a facile cascade of oxidation steps by first forming the 2-hydroxy-cyclohexadienyl oxyl radical VI. This intermediate is prone to ring opening via β-fragmentation and generates the open-chain delocalized 6-hydroxy-hexa-2,4-dienalyl radical VII, in which one terminus is the first carbonyl group of the final dialdehyde. The second one can form either by simple H abstraction operated by O2 or by O2 addition followed by HOO• elimination. The overall free-energy drop with respect to III is estimated to be 48 kcal mol-1. Exploration of other pathways, possibly playing a major role in yielding aldehydes in the case of low NO x concentration, indicates that only ring closure of the 2-hydroxy-cyclohexadienyl peroxyl radical III to the [3.2.1] bicyclic endo-peroxy allyl radical intermediate XIII is promising. In this case, however, the outcome of a subsequent ring opening can ultimately be the production of 1,2 and 1,4 dialdehydes (as direct oxidation of muconaldehyde itself can actually do).

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Section: Introductionmentioning

confidence: 99%

From Benzene to Muconaldehyde: Theoretical Mechanistic Investigation on Some Tropospheric Oxidation Channels

Ghigo

Tonachini

1999

J. Am. Chem. Soc.

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“…First, it can react with glutathione (GSH) to form S-phenylmercapturic acid (PMA) [57,58]. Second, in an iron-catalyzed ringopening reaction, it converted to trans,trans-muconic acid (tt-MA) [53,54,59].…”

Section: Benzenementioning

confidence: 99%

Benzene, toluene, ethylbenzene, and xylene: Current analytical techniques and approaches for biological monitoring

Soleimani

2020

Reviews in Analytical Chemistry

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Benzene, toluene, ethylbenzene, and xylene (BTEX) are a group of volatile organic compounds that human exposure to them may result in the development of some diseases, including cancer. Biological monitoring plays an important role in exposure assessment of workers occupationally exposed to chemicals. Several metabolites have been proposed for biological monitoring of individuals who are exposed to BTEX. There are a variety of extraction methods and analytical techniques for the determination of unmetabolized BTEX in exhaled air and their urinary metabolites. The present study aimed to summarize and review the toxicokinetics of BTEX and sample preparation and analytical methods for their measurement. Metabolites of BTEX are discussed to find out reliable ones for biological monitoring of workers exposed to these chemicals. In addition, analytical methods for unmetabolized BTEX in exhaled air and their metabolites were reviewed in order to obtain a comparison between them in term of selectivity, sensitivity, simplicity, time, environmental-friendly and cost. Given the recent trends in sample preparation, including miniaturization, automation, high-throughput performance, and on-line coupling with analytical instrument, it seems that microextraction techniques, especially microextraction by packed sorbents are the methods of choice for the determination of the BTEX metabolites.

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“…Reactive metabolites formed from benzene include benzene epoxide [13-15], trans, trans muconaldehyde [16-19], phenolic metabolites of benzene [20-22] which can give rise to oxygen radicals upon autoxidation [23;24], reactive quinones and semiquinones formed from polyphenolic metabolites of benzene [25-28] [29] and quinone thiol adducts [30;31] (Table 1). Consequently, the metabolism of benzene is complex and gives rise to a large number of potentially reactive products which have been suggested to be important in benzene toxicity.…”

Section: Reactive Metabolites and Metabolic Susceptibility Factorsmentioning

confidence: 99%

Relationships between metabolic and non-metabolic susceptibility factors in benzene toxicity

Ross

Zhou

2010

Chemico-Biological Interactions

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Reactive metabolites formed from benzene include benzene oxide, trans, trans muconaldehyde, quinones, thiol adducts, phenolic metabolites and oxygen radicals. Susceptibility to the toxic effects of benzene has been suggested to occur partly because of polymorphisms in enzymes involved in benzene metabolism which include cytochrome P450 2E1, epoxide hydrolases, myeloperoxidase, glutathione-S-transferases and quinone reductases. However, susceptibility factors not directly linked to benzene metabolism have also been associated with its toxicity and include p53, proteins involved in DNA repair, genomic stability and expression of cytokines and/or cell adhesion molecules. In this work, we examine potential relationships between metabolic and non-metabolic susceptibility factors using the enzyme NAD(P)H:quinone oxidoreductase (NQO1) as an example. NQO1 may also impact pathways in addition to metabolism of quinones due to protein-protein interactions or other mechanisms related to NQO1 activity. NQO1 has been implicated in stabilizing p53 and in maintaining microtubule integrity. Inhibition or knockdown of NQO1 in bone marrow endothelial cells has been found to lead to deficiencies of E-selectin, ICAM-1 and VCAM-1 adhesion molecule expression after TNFα stimulation. These examples illustrate how the metabolic susceptibility factor NQO1 may influence non-metabolic susceptibility pathways for benzene toxicity. KeywordsBenzene; metabolic susceptibility factors; p53; NQO1; adhesion molecules; bone marrow endothelial cells Metabolic factors in susceptibility to benzene toxicityBenzene induces hematopoietic toxicity and can induce aplastic anemia, myelodysplasia and acute myeloid leukemia after chronic exposure [1;2]. The metabolism of benzene has been investigated extensively and previous reviews have characterized benzene metabolism in a comprehensive manner [3][4][5][6][7]. Consequently, this work is not intended to be a review of benzene metabolism but will focus on metabolic susceptibility factors for benzene toxicity which have been identified in both cell and animal studies and in studies of occupationally-exposed populations. Other susceptibility factors not directly linked to metabolism have also been Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. identified in benzene toxicity and relationships between metabolic and non-metabolic susceptibility factors have not been previously considered. We will therefore discuss potential relationships between these two groups of susceptibility factors using the enzyme NAD(P) H:quinone oxidoreductase 1 (NQO1) as an example and hi...

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Chemistry of Muconaldehydes of Possible Relevance to the Toxicology of Benzene

Cited by 9 publications

References 5 publications

From Benzene to Muconaldehyde: Theoretical Mechanistic Investigation on Some Tropospheric Oxidation Channels

From Benzene to Muconaldehyde: Theoretical Mechanistic Investigation on Some Tropospheric Oxidation Channels

Benzene, toluene, ethylbenzene, and xylene: Current analytical techniques and approaches for biological monitoring

Relationships between metabolic and non-metabolic susceptibility factors in benzene toxicity

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