The role of p53 in spontaneous and radiation-induced apoptosis in the gastrointestinal tract of normal and p53-deficient mice.
Three h after whole-body irradiation (8 Gy) of C57BL x DBA/2 F1 mice, p53 protein was expressed strongly in the stem cell compartment of the small intestine but at lower levels in the colon. At this time, apoptotic cells were also observed in the stem cell position of the small intestine, with fewer in the colon. In mice without copies of the p53 gene (nulls), the levels of spontaneous apoptosis, in both the small intestine and the colon, were not different from wild-type. Irradiation of the nulls with 8 Gy of gamma-rays failed to induce any further apoptosis: the loss of p53 essentially rendered the epithelial cells, from both the small intestine and the colon, radioresistant. The response of the epithelial stem cells of the small intestine suggests that p53 may play a role in the deletion of damaged cells with carcinogenic potential, whereas this process is limited in the colon.
Merritt
A J
AJ
CRC Department of Epithelial Biology, Paterson Institute for Cancer Research, Christie Hospital (NHS) Trust, Manchester, United Kingdom.
Potten
C S
CS
Kemp
C J
CJ
Hickman
J A
JA
Balmain
A
A
Lane
D P
DP
Hall
P A
PA
D000818:Animals; D017209:Apoptosis / Q000502:physiology* / Q000528:radiation effects*; D003106:Colon / Q000473:pathology / Q000528:radiation effects; D003110:Colonic Neoplasms / Q000473:pathology; D004064:Digestive System / Q000473:pathology / Q000528:radiation effects*; D004068:Digestive System Physiological Phenomena; D004848:Epithelium / Q000473:pathology / Q000502:physiology / Q000528:radiation effects; D015994:Incidence; D007414:Intestinal Neoplasms / Q000473:pathology; D007420:Intestine, Large / Q000473:pathology / Q000502:physiology / Q000528:radiation effects; D007421:Intestine, Small / Q000473:pathology / Q000502:physiology / Q000528:radiation effects; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D009381:Neoplasms, Radiation-Induced / Q000473:pathology; D013997:Time Factors; D016159:Tumor Suppressor Protein p53 / Q000172:deficiency* / Q000502:physiology*; D014916:Whole-Body Irradiation
D016159:Tumor Suppressor Protein p53