Mercapturic acids revisited as biomarkers of exposure to reactive chemicals in occupational toxicology: a minireview

Haufroid, Vincent; Lison, Dominique

doi:10.1007/s00420-005-0620-z

Cited by 40 publications

(34 citation statements)

References 70 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In particular, a class of excreted metabolites, N-acetyl-L-cysteine thioethers (mercapturic acids), the formation of which by chemical or enzyme-catalyzed reaction of electrophiles with glutathione is very close to that of the adducts at the cysteine thiol group in proteins, has recently gained much interest both in occupational toxicology (Haufroid & Lison, 2005) and in metabolomics. Selective detection of this class of metabolites in urine can be accomplished by coupling HPLC separation with negative-ion constant neutral loss scanning mass spectrometry (Scheme 16) (Scholz et al, 2005;Wagner et al, 2006Wagner et al, , 2007.…”

Section: Mass Spectrometry and Protein Adductsmentioning

confidence: 99%

Toward an “omic” physiopathology of reactive chemicals: Thirty years of mass spectrometric study of the protein adducts with endogenous and xenobiotic compounds

Rubino

Pitton

Fabio

et al. 2009

Mass Spectrometry Reviews

109

170

View full text Add to dashboard Cite

Cancer and degenerative diseases are major causes of morbidity and death, derived from the permanent modification of key biopolymers such as DNA and regulatory proteins by usually smaller, reactive molecules, present in the environment or generated from endogenous and xenobiotic components by the body's own biochemical mechanisms (molecular adducts). In particular, protein adducts with organic electrophiles have been studied for more than 30 [see, e.g., Calleman et al., 1978] years essentially for three purposes: (a) as passive monitors of the mean level of individual exposure to specific chemicals, either endogenously present in the human body or to which the subject is exposed through food or environmental contamination; (b) as quantitative indicators of the mean extent of the individual metabolic processing which converts a non-reactive chemical substance into its toxic products able to damage DNA (en route to cancer induction through genotoxic mechanisms) or key proteins (as in the case of several drugs, pesticides or otherwise biologically active substances); (c) to relate the extent of protein modification to that of biological function impairment (such as enzyme inhibition) finally causing the specific health damage. This review describes the role that contemporary mass spectrometry-based approaches employed in the qualitative and quantitative study of protein-electrophile adducts play in the discovery of the (bio)chemical mechanisms of toxic substances and highlights the future directions of research in this field. A particular emphasis is given to the measurement of often high levels of the protein adducts of several industrial and environmental pollutants in unexposed human populations, a phenomenon which highlights the possibility that a number of small organic molecules are generated in the human organism through minor metabolic processes, the imbalance of which may be the cause of "spontaneous" cases of cancer and of other degenerative diseases of still uncharacterized etiology. With all this in mind, it is foreseen that a holistic description of cellular functions will take advantage of new analytical methods based on time-integrated metabolomic measurements of a new biological compartment, the "adductome," aimed at better understanding integrated organism response to environmental and endogenous stressors.

show abstract

Section: Mass Spectrometry and Protein Adductsmentioning

confidence: 99%

Toward an “omic” physiopathology of reactive chemicals: Thirty years of mass spectrometric study of the protein adducts with endogenous and xenobiotic compounds

Rubino

Pitton

Fabio

et al. 2009

Mass Spectrometry Reviews

109

170

View full text Add to dashboard Cite

show abstract

“…Another possible pathway for ethylene oxide detoxification is the formation of ethylene glycol partly by epoxide hydrolase (EPHX1; refs. 2,12). Thus, carriers of GST or epoxide hydrolase genotypes with high enzyme activity may form more HEMA or ethylene glycol, respectively, and be better protected against ethylene oxide.…”

Section: Introductionmentioning

confidence: 99%

Exposure to Ethylene Oxide in Hospitals: Biological Monitoring and Influence of Glutathione S-Transferase and Epoxide Hydrolase Polymorphisms

Haufroid

Merz²,

Hofmann³

et al. 2007

Cancer Epidemiology, Biomarkers &Amp; Prevention

View full text Add to dashboard Cite

Ethylene oxide is considered as a human carcinogen. A biomarker of exposure would be a useful instrument to assess the risk in occupationally exposed workers. This cross-sectional study aimed at examining (a) whether the urinary excretion of a metabolite of ethylene oxide, 2-hydroxyethyl mercapturic acid (HEMA), could be used for monitoring occupational exposure and (b) whether glutathione S-transferase (GST) and epoxide hydrolase genotypes influenced biological monitoring. Exposure to ethylene oxide was measured by personal sampling in 80 hospital workers (95% of those eligible). HEMA concentrations were determined in three urine samples (baseline, end of shift, and next morning) by liquid chromatography with tandem mass spectrometry. GSTs (GSTT1, GSTM1, and GSTP1) and epoxide hydrolase (EPHX1) were also genotyped. The influence of exposure, genotypes, and several other factors was examined in multiple regression analyses. Exposure was always <1 parts per million. On a group basis, exposure and a non-null GSTT1 genotype increased the HEMA concentrations in the urine sample collected at the end of the shift and these factors remained statistically significant after considering possible confounding or modifying factors. (Cancer Epidemiol Biomarkers Prev 2007;16(4):796 -802)

show abstract

“…The conjugation of benzene oxide and glutathione forms a pre-mercapturic acid, which is further metabolized in kidneys yielding S-phenylmercapturic acid [13]. Recent studies confirm the usefulness of mercapturic acids as a biological exposure index for electrophilic chemicals [14]. Determining thioethers in urine samples is a noninvasive method for detecting occupational exposure to benzene and other alkilating agents.…”

Section: Introductionmentioning

confidence: 99%

Effect of Simultaneous Exposure to Benzene and Ethanol on Urinary Thioether Excretion

Mikov

Stankov

Vasović

et al. 2012

International Journal of Occupational Safety and Ergonomics

View full text Add to dashboard Cite

Mercapturic acids revisited as biomarkers of exposure to reactive chemicals in occupational toxicology: a minireview

Cited by 40 publications

References 70 publications

Toward an “omic” physiopathology of reactive chemicals: Thirty years of mass spectrometric study of the protein adducts with endogenous and xenobiotic compounds

Toward an “omic” physiopathology of reactive chemicals: Thirty years of mass spectrometric study of the protein adducts with endogenous and xenobiotic compounds

Exposure to Ethylene Oxide in Hospitals: Biological Monitoring and Influence of Glutathione S-Transferase and Epoxide Hydrolase Polymorphisms

Effect of Simultaneous Exposure to Benzene and Ethanol on Urinary Thioether Excretion

Contact Info

Product

Resources

About