Estimation of exposure to alkylating carcinogens by the GC-MS determination of adducts to hemoglobin and nucleic acid bases in urine

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Abstract
Many carcinogens and mutagens are electrophilic in nature and will react with nucleophilic sites in protein and nucleic acid. Determination of the extent of formation of these adducts of genotoxic agents with protein provides a practical method of monitoring human exposure and of determining the possible risk associated with the exposure. Proteins are predominately attacked on the cysteine, histidine and N-terminal amino acids. Hemoglobin is the most suitable protein for dose monitoring due to its ready availability and its long lifetime. Methods have been developed using capillary gas chromatography with mass spectrometry for determining S-methylcysteine, Nr-[2-hydroxyethyl]histidine and Nr-[2-hydroxypropyl]histidine in hemoglobin, allowing the monitoring of in vivo exposure of laboratory animals and humans to methylating agents, ethylene oxide and propylene oxide, respectively. A method for monitoring exposure to acrylamide has also been devised based on the determination by gas chromatography-mass spectrometry of the adduct formed with cysteine residues in hemoglobin. An alternative method of dose monitoring of some methylating agents by the measurement of the urinary N-7-methylated guanine derived from alkylated DNA breakdown products has also been investigated.

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