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Figure 1 | Cancer Cell International

Figure 1

From: Stem cells, senescence, neosis and self-renewal in cancer

Figure 1

Fate of cells exposed to genotoxins: Immediate effect of exposure to genotoxins is the arrest of cell cycle progression. Cells with lethal damage will undergo necrotic death immediately or may commit immediate or delayed suicide by programmed cell death or apoptosis. Adaptation I. Some cells with minimal damage may re-enter cell cycle after some delay and repair of damage, and multiply normally without any immediate phenotypic changes. It is likely that some of these cells may carry epigenetic alterations and undergo neosis after a latent period of accumulation of additional damage to the genome. Adaptation Ii. Some cells become tetraploid due to cytokinesis failure. Some of them may commit apoptosis, or undergo mitotic catastrophe due to active mitotic checkpoint; such cells often form micronuclei during death. Some of them may undergo successfully multipolar mitosis, giving rise to aneuploid cells, which may not survive to give rise to clonal population of tumor cells. Adaptation III. A major fraction of cells enter a premature senescent phase due to genotoxin-induced DNA damage; by about a week or so, they express senescent markers such as SA-β-gal and SAHF in order to suppress tumor growth; they may become polyploid by endomitosis ad endoreduplication. Most of them may eventually die. Adaptation IV. By about second week after exposure to genotoxins, a few of the tetraploid and polyploid cells with genetic or epigenetic alterations in the senescence pathway may undergo neosis to give rise to aneuploid Raju cells with transient stemness. These are the precursors of primary tumor growth with extended MLS. They mature into tumor cells. At the end of their limited MLS, they reach senescent phase and undergo S/T-neosis and repeat the cycle of extended MLS, senescence, mitotic crisis and neosis several times, thus rejuvenating the supply of resistant (malignant) Raju cells in a highly non-synchronous fashion. (See the text for further details).

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