RE: cumulative apoptosis

I propose a new model in my dissertation to estimate Cumulative data (e.g.
Cumulative apoptotic index: CAI) using the time-course kinetics data (e.g.
apoptotic index: AI) based on measuring AI at multiple time points. I assume
that apoptosis may progress with multiple phases and the time-window (Tw) is
constant in all phases. Several variables are also introduced: the apoptotic
induction rate (percent apoptotic cells / hour) (AIRi, i= 1, 2, 3 etc) and
the time of each phase (Ti, i= 1, 2, 3 etc). 
	The kinetics of apoptosis are explained as follows: first, the shape
of the AI time-dependent curve is a guideline for how many phases of
apoptosis exist. When the graph is symmetrical, apoptosis take place in a
uni-phasic mode. If not, it could have bi- or multi-phasic modes. Second,
the number of plateau regions indicates how many different apoptotic phases
exist. One plateau or peak indicates there is at least one phase in AI data.
Third, the time-window (Tw), which can be different in different assays and
different cell lines, is calculated.  Fourth, the apoptotic induction rate
(AIRi, i= 1, 2, 3 etc) of each phase is calculated. Fifth, the length of
each phase (Ti, i= 1, 2, 3 etc) is calculated. There are three assumptions
which I have made for the CAI estimation. First, cells which start apoptosis
early exit the time-window early (first in, first out). Second, the
time-window is a constant width within each phase. Third, the apoptotic
induction rate (AIRi) is equal to the rate of movement out of the time
window. Thus, it should show a linear symmetrical shape in each individual
phase.	This analysis is very similar to the concept of Fraction of Labeled
Mitoses curves where cells move into and out of a mitotic window, but in
this case they are apoptotic windows and multiple phases can exist.


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Chang-Uk Lim						    
Cell and Molecular Biology Program
Environmental & Radiological Health Sciences

Colorado State University

905 W. Laurel St. Apt 221
Fort Collins, CO. 80521 USA
H)970-492-9115 O)970-491-3681 Fax) 970-491-0623
peterlim@lamar.colostate.edu

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