Exposure biomarkers for the study of toxicological impact on carcinogenic processes

Abstract

Exposure biomarkers for carcinogens in humans include the measurement of the genotoxin or its active metabolite in blood, urine or other tissues, and the determination of the interaction products (adducts) of the carcinogen with protein or DNA. The latter approach may indicate the amount of genotoxically active material that has reached the tissue under study and provides invaluable information for molecular epidemiological studies. Protein adducts are not repaired and are considered primarily as exposure monitors, but DNA adducts may give further information about the mutagenic significance of the exposure. The techniques available for measurement of protein and DNA adducts include mass spectrometry, immunoassay, high performance liquid chromatography with UV, fluorescence or electrochemical detection, 32P-postlabelling (for DNA only) and accelerator mass spectrometry. The lowest limits of sensitivity of the protein adduct measurements is less than 1 pmol adduct/g protein, and the procedures for DNA adduct determination have sensitivities ranging from of 1 adduct in 10(8) to 1 in 10(11) nucleotides. All these techniques are capable of measuring environmental, occupational and dietary exposures to a variety of genotoxic compounds, as exemplified in this review.