Stem cell kinetics and intestinal cancer.
The conventional view that intestinal stem cells divide every few days so that each stem cell undergoes several thousand divisions in a lifetime is challenged. It is proposed that fully differentiated cells, even in old age, are no more than sixty divisions from the zygote. This concept leads to a model in which the intestinal crypts are maintained by a linear hierarchy of stem cells. The model is consistent with experimental data on the clonal origin of intestinal crypts and the observed crypt mutant frequency following exposure to chemical carcinogens. It also provides an explanation for an important paradox in cancer which is that cancer incidence rises rapidly with age but less rapidly with carcinogen dose even though both are thought to act through the same mechanism.
Department of Pathology, Royal Lancaster Infirmary, U.K.
J A
JA
Morris
D000368:Aged; D000375:Aging / Q000502:physiology; D000818:Animals; D002453:Cell Cycle / Q000502:physiology; D006801:Humans; D007414:Intestinal Neoplasms / Q000209:etiology* / Q000235:genetics / Q000473:pathology*; D007422:Intestines / Q000166:cytology*; D008297:Male; D051379:Mice; D008954:Models, Biological; D009154:Mutation; D013234:Stem Cells / Q000166:cytology*