Journal article
A model of heat-induced clonogenic cell death
Journal of theoretical biology, Vol.156(2), pp.133-146
1992
DOI: 10.1016/S0022-5193(05)80669-1
PMID: 1640720
Abstract
When cells are exposed to elevated temperatures, clonogenicity decreases in a temperature-dependent manner displaying non-linear kinetics. In this report we show that the survival of synchronized cell populations after heat exposure can be characterized by a parameter
ε, which is normally-distributed throughout the population. Cells whose corresponding
ε-value lies below an arbitrary threshold value
ε
min are unable to form a colony. Upon transfer of a cell culture to an elevated temperature, the mean value of the
ε distribution decreases exponentially over time with a rate dependent upon the difference between the current and final mean value, until reaching a final value
ε
¯
f
dependent on the particular temperature used, thus representing a larger proportion of cells with
ε <
ε
min which are non-clonogenic. The analyses evaluate a temperature-independent parameter
k which is presumed to be dependent upon the growth conditions of the cell population, and a temperature-dependent parameter
ε
¯
f
, which is characteristic of the new temperature-perturbed steady state. Comparison of the results of analysis of synchronized
G
1 cell survival data to that for
S phase cells obtained over a range of temperatures shows that it is sufficient to ascribe the increased thermal sensitivity of
S phase cells to a different
k value, the temperature-dependence of
ε
¯
f
being identical in the two cases. Linear regression analysis of the temperature-dependence of
ε
¯
f
, when expressed as ln (−
ε
¯
f
) =
a
0 +
a
1/
T demonstrated strong linearity (
r
2 = 0·99) for either the individual (
G
1 or
S) or combined data sets. This description of heat-induced cytotoxicity may be of use as the basis for a dose concept for the clinical administration of hyperthermia.
Details
- Title: Subtitle
- A model of heat-induced clonogenic cell death
- Creators
- Michael A MackeyJoseph L Roti Roti
- Resource Type
- Journal article
- Publication Details
- Journal of theoretical biology, Vol.156(2), pp.133-146
- Publisher
- Elsevier Ltd
- DOI
- 10.1016/S0022-5193(05)80669-1
- PMID
- 1640720
- ISSN
- 0022-5193
- eISSN
- 1095-8541
- Language
- English
- Date published
- 1992
- Academic Unit
- Roy J. Carver Department of Biomedical Engineering; Radiology
- Record Identifier
- 9984064572502771
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