Apoptosis in oral mucosa: lessons from the crypt. A commentary.
The programmed removal of individual isolated cells from a tissue during development, in the adult steady state, and in pathological abnormalities, is an important regulated process that counter-balances the cells produced due to cell division, and compliments differentiation in the overall tissue homeostatic mechanisms. In stratified epithelium, apoptosis can sometimes be difficult to identify and end-labelling techniques such as TUNEL are difficult to optimise and validate. In the columnar epithelium of the small intestine, apoptosis is easy to recognise by virtue of the morphological changes seen in dying cells in routine paraffin sections. The dying cells fragment and the apoptotic fragments can be reliably counted. Because of the precise cell positional relationship between hierarchical status in the lineage and cell position in the tissue, the cell death can be related to the hierarchical status of the dying cells. In the normal steady state in healthy epithelium a small proportion of stem cells are constantly dying. This p53-independent apoptosis is interpreted as part of the homeostatic regulation of stem cell numbers. After exposure to low levels of genotoxic agents, such as radiation, some stem cells in this tissue are very susceptible to apoptosis induction in a p53-dependent fashion. This has been interpreted to be a genome protective mechanism that accounts at least in part for the unexpected low incidence of cancer in this rapidly proliferating, large mass of tissue within the gastrointestinal tract.
Potten
C S
CS
CRC Epithelial Biology Department, Paterson Institute for Cancer Research, Christie Hospital NHS Trust, Wilmslow Road, Manchester M20 4BX, UK. cpotten@picr.man.ac.uk
D000328:Adult; D000818:Animals; D017209:Apoptosis / Q000235:genetics / Q000502:physiology*; D016923:Cell Death / Q000235:genetics / Q000502:physiology; D002454:Cell Differentiation / Q000502:physiology; D002455:Cell Division / Q000502:physiology; D019070:Cell Lineage / Q000502:physiology; D004847:Epithelial Cells / Q000166:cytology / Q000502:physiology / Q000528:radiation effects; D016158:Genes, p53 / Q000235:genetics / Q000528:radiation effects; D006706:Homeostasis / Q000502:physiology; D006801:Humans; D020287:In Situ Nick-End Labeling; D007413:Intestinal Mucosa / Q000166:cytology* / Q000502:physiology / Q000528:radiation effects; D007414:Intestinal Neoplasms / Q000473:pathology; D051379:Mice; D009061:Mouth Mucosa / Q000166:cytology* / Q000502:physiology; D016612:Paraffin Embedding; D013234:Stem Cells / Q000166:cytology / Q000502:physiology / Q000528:radiation effects