No abstract

The growth kinetics of a cancer cell population as a function of the total number of cells and the proportion of proliferating and resting cells at the beginning of the growth has been analysed by a mathematical model. The model takes into account the processes of cell division, death and transition from proliferation to rest and backwards. It is shown that a single cell population growing under the same environmental conditions has an extremely broad spectrum of growth patterns. The whole multiplicity of possible growth patterns has been determined by the inherent cellular growth characteristics of the population, while the growth pattern actually realized of the variety of growth curves depends on the total number of cells and the proportion of proliferating and resting cells at the initial moment of growth. The model is shown to provide a good prediction of experimentally measured kinetics of regrowth of tumour cells subcultured after various times of the growth in unfed cultures, and the kinetics of tumour cell growth after severe hypoxia. The role of cell transitions between proliferating and resting stages in the problem of growth control is discussed.

Olivomycin (DNA-binding antibiotic) in nanomolar concentrations induces apoptosis of human tumor cells and inhibits p53-dependent transcription of the reporter gene (basal and induced by antitumor drugs). Olivomycin aglycon induces no cytotoxicity and does not block transcription.

A new method of stratification analysis of general populations is proposed that is based on the approximation of inverse empirical distribution functions. With the help of the methods developed, it is shown that the number of modal classes in a heterogeneous population equals the number of segments of a linear regression spline. The proposed method is used for the investigation of populations of cancer cells that are sensitive or resistant to cisplatin.