Fig. 1.

Mechanism of apoptosis induction in oncogenically transformed cells through signalling by surrounding cells (intercellular induction of apoptosis; reviewed in ref. 8). Panel A: Three steps in the mechanism of intercellular induction of apoptosis and their representation in the model. In step 1, transformed cells trigger, through TGF-β signalling, the release of POD and NO^· in neighbour cells, which thus become effector cells with respect to intercellular induction of apoptosis; also transformed cells themselves may serve as effector cells and release these species (dashed arrows). In step 2, a cascade of biochemical reactions occur between superoxide (O₂ ^{− ·}) produced by transformed cells and POD and NO^· released by effector cells, leading to production of ·OH in the vicinity of transformed cells. The two major pathways of the biochemical signalling cascade are depicted in detail in panel B; this work is focused on the HOCl pathway, highlighted in boldface. Finally, in step 3, the attacks of ·OH damage cellular membrane, which initiates an intracellular signalling pathway leading to apoptosis. In the model described in this paper, per-cell release rates of signalling species are considered in step 1, a set of reaction–diffusion equations is used to model step 2, and step 3 is represented by a non-linear kinetic model in which induction of apoptosis competes with cell proliferation.