SOMATIC MUTATION DETECTION IN HUMAN BIOMONITORING

Somatic cell gene mutation arising in vivo may be considered to be a b iomarker for genotoxicity. Assays detecting mutations of the haemoglob in and glycophorin A genes in red blood cells and of the hypoxanthine- guanine phosphoribosyltransferase and human leucocyte antigenes in T-l ymphocytes are available in humans. This MiniReview describes these as says and their application to studies of individuals exposed to genoto xic agents. Moreover, with the implementation of techniques of molecul ar biology mutation spectra can now be defined in addition to the quan titation of in vivo mutant frequencies. We describe current screening methods for unknown mutations, including the denaturing gradient gel e lectrophoresis, single strand conformation polymorphism analysis, hete roduplex analysis, chemical modification techniques and enzymatic clea vage methods. The advantage of mutation detection as a biomarker is th at it integrates exposure and sensitivity in one measurement. With the analysis of mutation spectra it may thus be possible to identify the causative genotoxic agent.