ABSTRACT
As detailed throughout this book and elsewhere (1,2), there are several dif-
ferent ways in which cells can die after injury, including that produced by
conventional anticancer therapy. In many cases, cells manifest more than one
mode of cell death following a given treatment (3). The mix of the different
modes of cell death depends critically on the type of cell, its genetic makeup,
and the agent used. For example, B-lymphocytes are particularly susceptible
to dying by apoptosis, whereas cells derived from epithelial or connective
tissues are more likely to experience mitotic death or be permanently arrested
following DNA damage (1,4-7). What is perhaps less appreciated is the
importance of the dose delivered to the cells in determining the mode of cell
death. This is well illustrated in Figure 1, which shows the cumulative per-
centage of apoptosis in the human TK6 B-lymphocyte cell line as a function of
radiation dose. Though this cell line is particularly susceptible to death by
apoptosis, it is even more sensitive to cell inactivation measured by clono-
genic survival probably because of the sensitivity of this cell line to mitotic
death as a result of a deficiency in DNA double strand break repair (8). As
shown in Figure 1A, a dose of 5 Gy kills approximately 50% of the cells by
apoptosis. However, Figure 1B shows that few, if any, cells survive this dose
when measured by clonogenic survival. At a lower dose (e.g., 2 Gy), few cells
(<10%) die of apoptosis, but more than 90% die by clonogenic survival. Thus, at high doses (>5 Gy), most cells die of apoptosis, but at lower doses, another form of cell death predominates.
