Variation in the baseline sister chromatid exchange frequency in human lymphocytes

The utility of the sister chromatid exchange (SCE) assay for human population studies is potentially limited by the variability associated with individual baseline SCE frequencies. This investigation identifies and quantifies the major sources of preparative and biological variation associated with the determination of baseline SCE frequencies in cultured human lymphocytes. Much of the variation in lymphocyte SCE frequencies is attributable to the amount of bromodeoxyuridine (BrdUrd) available per lymphocyte; the pooled coefficient of variation (CV) over the dose range of 10 to 160 μM is about 18%. Other variations in the baseline frequency result from culture‐to‐culture and slide‐to‐slide differences. The pooled coefficient of variation among donors is about 10%. The effect of cell‐to‐cell differences in baseline SCE frequency among donors can be minimized by increasing the number of cells scored per donor. When 20 cells are analyzed per individual the pooled cell‐to‐cell variation is 9% but when 40 or 80 cells are analyzed it is reduced to 6 and 4% respectively. For a single individual the cell‐to‐cell coefficient of variation at 100 μM BrdUrd is 40.8%. Under our experimental conditions, a 30% increase in SCE frequency between two cohort populations can be detected with a 95% probability at a 5% level of significance when 11 individuals per cohort are studied. For a longitudinal or in vitro dose response study of a single individual, a 50% increase in SCE frequency can be detected with a 95% probability at a 5% level of significance when 25 cells per sample are analyzed. These results indicate the feasibility of applying the SCE bioassay to humans as a measure of environmental stress.