Carcinogen adducts: use in diagnosis and risk assessment

Abstract

Exposure to genotoxic carcinogens results in the formation of covalently bound adducts of the carcinogens with cellular nucleophilic molecules, including DNA and protein. Quantitative measurements of these adducts may be used to monitor exposure to these carcinogens. The analytical methods required to detect the adducts need to be of exceptional sensitivity and include 32P-postlabeling, immunoassay, and physicochemical techniques (e.g., mass spectrometry or fluorescence measurements). Owing to its accessibility and long lifetime, hemoglobin is also suitable for carcinogen adduct measurement, and techniques based on gas chromatography-mass spectrometry or immunoassay have been developed for this purpose. Although the measurement of adducts is now accepted as a valid means of monitoring exposure to carcinogens, the value of such measurements in indicating carcinogenic risk in humans is less certain. However, adduct concentrations, particularly at low doses of carcinogen, have in several instances been shown to correlate with tumorigenicity in animal experiments.