Need for Single-Cell Monitoring

Assays that measure end points for cell populations rather than multiple individual cells might produce contradictory findings. These occur due to a failure to discriminate and correct for confounding effects of extracellular staining, dead cells, different cell types, or opposite effects in different cells. 

For example, mitochondrial reductive capacity is decreased with decreased cell numbers but is increased with cells that are activated, such as lymphocytic immune activation, or if cells adapt to the stress associated with toxicity, such as during mitochondrial biogenesis. Thus, mitochondrial reductive capacity might be either increased or decreased with toxicity. Similar contradictory interpretations might occur with other cellular activities, for which there is a compensatory adaptive increase before their failure. This biphasic change is referred to as hormesis and occurs not only with reductive mitochondrial activity but also with mitochondrial number, cell number, mitochondrial membrane potential, antioxidant system activity and numerous other activities. 

Finally, individual cell studies might be more accurate than cell population studies in which responses are variable over time or over different cells. Analysis of the sequence of changes in the different parameters might be important in elucidating the mechanisms and pathogenesis of toxicity. 

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