Use of cytogenetic endpoints in human lymphocytes as indicators of exposure to genotoxicants

Since the observation by Moorhead et al (1960) that peripheral lymphocytes could be stimulated by phytohemagglutinin (pha) to enter the cell cycle and observed at metaphase, there has been an enormous amount of data obtained on the induction of chromosome alterations by radiation and chemical agents with this lymphocyte assay system. It has generally been regarded as a simple and informative assay for human population monitoring, as an aid to providing information on potential clastogenic (or mutagenic) exposures. As will be suggested, this view should be regarded with great caution with regard to chemical exposures, particularly in contrast to radiation exposures. It is premature to assume that information on the level of exposure or subsequent adverse health effects can be ascertained or determined from measures of chromosome alteration frequencies or sister chromatid exchange frequency in mitogenically stimulated human peripheral lymphocytes. This chapter will address the issue of the utility of the lymphocyte assay, with reference to the underlying mechanisms of induction of chromosome alterations, and also will discuss possible ways of increasing the sensitivity of the assay in order to make it more useful for population monitoring. 29 references