  Objectives: In this study, we quantify the growth variability of tumour cell
clones from a human leukemia cell line. Materials and methods: We have used
microplate spectrophotometry to measure the growth kinetics of hundreds of
individual cell clones from the Molt3 cell line. The growth rate of each clonal
population has been estimated by fitting experimental data with the logistic
equation. Results: The growth rates were observed to vary among different
clones. Up to six clones with a growth rate above or below the mean growth rate
of the parent population were further cloned and the growth rates of their
offsprings were measured. The distribution of the growth rates of the subclones
did not significantly differ from that of the parent population thus suggesting
that growth variability has an epigenetic origin. To explain the observed
distributions of clonal growth rates we have developed a probabilistic model
assuming that the fluctuations in the number of mitochondria through successive
cell cycles are the leading cause of growth variability. For fitting purposes,
we have estimated experimentally by flow cytometry the maximum average number
of mitochondria in Molt3 cells. The model fits nicely the observed
distributions of growth rates, however, cells in which the mitochondria were
rendered non functional (rho-0 cells) showed only a 30% reduction in the clonal
growth variability with respect to normal cells. Conclusions: A tumor cell
population is a dynamic ensemble of clones with highly variable growth rate. At
least part of this variability is due to fluctuations in the number of
mitochondria.
