ABSTRACT
The organization of a high-turnover epithelial tissue into self-renewing crypt units that are
maintained by a small number of resident but pluripotent stem cells provides a protective
environment for cancer induction. In the intestine, two important principles appear to be at
work: the first one, suggested by Cairns (1,2), relates to the preferential segregation of
DNA strands in the stem cells preventing (or minimizing) the accumulation of DNA repli-
cation errors. Experimental evidence for this mechanism has recently been proffered by
Potten et al. (3). The genomic integrity of stem cells may be further protected by an over-
riding apoptotic response to DNA damage, rather than being permissive to misrepair of
DNA damage. The second principle relates to the transport of stem-cell progeny by the
crypt “conveyor belt”, which is driven by proliferating transient cells above the stem
cell compartment (4). The implications of these two principles, their incorporation into
quantitative models of crypt dynamics and carcinogenesis, and how cancer circumvents
these protective mechanisms, are important issues that have only come into focus more
recently in experimental studies and their mathematical analysis. Here we describe a
simple multistage carcinogenesis model for the development of colon cancer, however
a model that is consistent with the role of stem cells in maintaining tissue (and crypt) archi-
tecture (Chap. 6).
