Mercapturic Acids, Protein Adducts, and DNA Adducts as Biomarkers of Electrophilic Chemicals

Abstract

The possibilities and limitations of using mercapturic acids and protein and DNA adducts for the assessment of internal and effective doses of electrophilic chemicals are reviewed. Electrophilic chemicals may be considered as potential mutagens and/or carcinogens. Mercapturic acids and protein and DNA adducts are considered as selective biomarkers because they reflect the chemical structure of the parent compounds or the reactive electrophilic metabolites formed during biotransformation. In general, mercapturic acids are used for the assessment of recent exposure, whereas protein and DNA adducts are used for the assessment of semichronic or chronic exposure. 2-Hydroxyethyl mercapturic acid has been shown to be the urinary excretion product of five different reactive electrophilic intermediates. Classification of these electrophiles according to their acid-base properties might provide a tool to predict their preference to conjugate with either glutathione and proteins or with DNA. Constant relationships appear to exist in the cases of 1,2-dibromoethane and ethylene oxide between urinary mercapturic acid excretion and DNA and protein adduct concentrations. This suggests that mercapturic acids in some cases may also play a role as a biomarker of effective dose. It is concluded that simultaneous determination of mercapturic acids, protein and DNA adducts, and other metabolites can greatly increase our knowledge of the specific roles these biomarkers play in internal and effective dose assessment. If the relationship between exposure and effect is known, similar to protein and DNA adducts, mercapturic acids might also be helpful in (individual) health risk assessment.

Reference range concentrations of N-acetyl-S-(2-hydroxyethyl)-L -cysteine, a common metabolite of several volatile organic compounds, in the urine of adults in the United States

“…Reference range values for VC, EO, and EDB are not known. The purpose of our study was to determine the reference range concentrations for N-acetyl-S-(2-hydroxyethyl)-L-cysteine (2-hydroxyethyl mercapturic acid, HEMA), a urinary metabolite of VC, EO, EDB, acrylonitrile (ACN), and other electrophilic compounds with a twocarbon backbone (Van Bladeren et al, 1981;Linhart et al, 1988;Vermeulen et al, 1989;Van Welie et al, 1992). HEMA has been used as a biomarker of exposure to EO and other VOCs in animals (Gerin and Tardif, 1986;Gerin et al, 1988;Tardif et al, 1987) and also in humans (Popp et al, 1994).…”

Total plasma protein adducts of allergenic hexahydrophthalic and methylhexahydrophthalic anhydrides as biomarkers of long-term exposure

“…In the monitoring of exposure to carcinogenic compounds, protein adducts are often considered to be biomarkers of effective dose (ie, they indicate the dose of the compound at the target site) (20). The formation of protein adducts from allergenic, low-molecular-weight chemicals is believed to be an important step in the IgE sensitization process.…”

“…In contrast, HSA may constitute a better index of integrated cumulative exposure, as it is easily accessible by the xenobiotics and is also abundant. Several methods have been published on the quantification of HSA adducts of various compounds (19)(20)(21). The common drawback in all these procedures is the laborious and tedious protein purification steps that make the methods impractical for bulk routine use.…”

Metabotype Concept: Flexibility, Usefulness and Meaning in Different Biological Populations

“…Adducts such as N-(2-hydroxyethyl)valine have also been detected in haemoglobin from hospital workers exposed to ethylene oxide (Van Welie et al, 1992).…”

“…Oxidative damage to DNA can be detected by urinary 8-hydroxy-2'-deoxyguanosine (Van Welie et al, 1992). Also, urinary 8-hydroxy-2'-deoxyguanosine has been proposed as a biomarker of oxidative stress in humans (Bianchini et al, 1996).…”