Mercapturic acids, protein adducts, and DNA adducts as biomarkers of electrophilic chemicals.
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.
van Welie
R T
RT
Department of Pharmacochemistry, Vrije Universiteit, Amsterdam, The Netherlands.
van Dijck
R G
RG
Vermeulen
N P
NP
van Sittert
N J
NJ
D000111:Acetylcysteine / Q000737:chemistry*; D000818:Animals; D015415:Biomarkers; D004247:DNA / Q000737:chemistry*; D004563:Electrochemistry; D006801:Humans; D011506:Proteins / Q000737:chemistry*
D015415:Biomarkers; D011506:Proteins; D004247:DNA; D000111:Acetylcysteine