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[Cancer Research 54, 614-617, February 1, 1994]
© 1994 American Association for Cancer Research

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The Role of p53 in Spontaneous and Radiation-induced Apoptosis in the Gastrointestinal Tract of Normal and p53-deficient Mice1

Anita J. Merritt2, Christopher S. Potten3, Christopher J. Kemp4, John A. Hickman, Allan Balmain, David P. Lane and Peter A. Hall

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 {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.

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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J. Cell Sci.Home page
C. Midgley, B Owens, C. Briscoe, D. Thomas, D. Lane, and P. Hall
Coupling between gamma irradiation, p53 induction and the apoptotic response depends upon cell type in vivo
J. Cell Sci., January 5, 1995; 108(5): 1843 - 1848.
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Genes Dev.Home page
H Baribault, J Penner, R V Iozzo, and M Wilson-Heiner
Colorectal hyperplasia and inflammation in keratin 8-deficient FVB/N mice.
Genes & Dev., December 15, 1994; 8(24): 2964 - 2973.
[Abstract] [PDF]


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Genes Dev.Home page
A Di Leonardo, S P Linke, K Clarkin, and G M Wahl
DNA damage triggers a prolonged p53-dependent G1 arrest and long-term induction of Cip1 in normal human fibroblasts.
Genes & Dev., November 1, 1994; 8(21): 2540 - 2551.
[Abstract] [PDF]


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J. Cell Sci.Home page
P. Hall, P. Coates, B Ansari, and D Hopwood
Regulation of cell number in the mammalian gastrointestinal tract: the importance of apoptosis
J. Cell Sci., January 12, 1994; 107(12): 3569 - 3577.
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Cold Spring Harb Symp Quant BiolHome page
A.H. Wyllie, P.J. Carder, A.R. Clarke, K.J. Cripps, S. Gledhill, M.F. Greaves, S. Griffiths, D.J. Harrison, M.L. Hooper, R.G. Morris, et al.
Apoptosis in Carcinogenesis: The Role of p53
Cold Spring Harb Symp Quant Biol, January 1, 1994; 59(0): 403 - 409.
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Cold Spring Harb Symp Quant BiolHome page
S.W. Lowe, S. Bodis, N. Bardees, A. McClatchey, L. Remington, H.E. Ruley, D.E. Fisher, T. Jacks, J. Pelletier, and D.E. Housman
Apoptosis and the Prognostic Significance of p53 Mutation
Cold Spring Harb Symp Quant Biol, January 1, 1994; 59(0): 419 - 426.
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Cold Spring Harb Symp Quant BiolHome page
W.F. Dove, C. Luongo, C.S. Connelly, K.A. Gould, A.R. Shoemaker, A.R. Moser, and R.L. Gardner
The Adenomatous Polyposis Coli Gene of the Mouse in Development and Neoplasia
Cold Spring Harb Symp Quant Biol, January 1, 1994; 59(0): 501 - 508.
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Proc. Natl. Acad. Sci. USAHome page
R. B. Halberg, D. S. Katzung, P. D. Hoff, A. R. Moser, C. E. Cole, R. A. Lubet, L. A. Donehower, R. F. Jacoby, and W. F. Dove
Tumorigenesis in the multiple intestinal neoplasia mouse: Redundancy of negative regulators and specificity of modifiers
PNAS, March 28, 2000; 97(7): 3461 - 3466.
[Abstract] [Full Text] [PDF]


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Proc. Natl. Acad. Sci. USAHome page
S. A. Maxwell and G. E. Davis
Differential gene expression in p53-mediated apoptosis-resistant vs. apoptosis-sensitive tumor cell lines
PNAS, November 21, 2000; 97(24): 13009 - 13014.
[Abstract] [Full Text] [PDF]




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