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CRC Department of Epithelial Biology, Paterson Institute for Cancer Research, Christie Hospital (NHS) Trust, Wilmslow Road, Manchester, M20 9BX [A. J. M., C. S. P.]; CRC Molecular and Cellular Pharmacology Group, School of Biological Sciences, University of Manchester, Stopford Building, Oxford Road, Manchester, M13 9PT [A. J. M., J. A. H.]; CRC Beatson Institute for Cancer Research, Garscube Industrial Estate, Switchback Road, Bearsden, Glasgow, G61 1BD [C. J. K., A. B.]; Department of Pathology, University of Dundee, Dundee, DD1 9SY [P. J. H.]; and CRC Cell Transformation Unit, Department of Biochemistry, University of Dundee, Dundee, DD1 4HN [D. P. L.] United Kingdom
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
-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.
1 This work was supported by the Cancer Research Campaign.
2 Supported by a graduate studentship from the Cancer Research Campaign.
3 To whom requests for reprints should be addressed.
4 We are grateful to the United Kingdom Combined Cancer Research Campaign for their support to C. J. K.
Received 11/10/93. Accepted 12/22/93.
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