Please use this identifier to cite or link to this item:
https://hdl.handle.net/2440/17488
Citations | ||
Scopus | Web of ScienceĀ® | Altmetric |
---|---|---|
?
|
?
|
Type: | Journal article |
Title: | Relationship between dose of methotrexate, apoptosis, p53/p21 expression and intestinal crypt proliferation in the rat |
Author: | Gibson, R. Bowen, J. Cummins, A. Keefe, D. |
Citation: | Research in Experimental Medicine, 2005; 4(4):188-195 |
Publisher: | Springer-Verlag Italia Srl |
Issue Date: | 2005 |
ISSN: | 1591-8890 1591-9528 |
Statement of Responsibility: | R.J. Gibson; J.M. Bowen; A.G. Cummins; D.M.K. Keefe |
Abstract: | Previous studies have shown that apoptosis is induced by cytotoxic chemotherapy and precedes hypoproliferation of intestinal crypt cells. However, the relationship between the degree of intestinal apoptosis and crypt cell hypoproliferation may not be directly related. The purpose of this study was to investigate the relationship between apoptosis and hypoproliferation with increasing doses of chemotherapy. Eleven groups of breast cancer-bearing DA rats were treated with two doses of methotrexate (MTX) i. m. at varying concentrations (0.5, 1.5, 2.5 and 5.0 mg/kg) or saline (control). Animals were killed at 6 or 24 h following treatment. The small and large intestines were examined for apoptosis, villous area (small intestine), crypt length and mitotic count per crypt. Immunohistochemical expression of p53 and p21waf1/cip1 (p21) were examined quantitatively. Data were analysed using Peritz F-test. Low dose MTX (0.5 mg/kg) did not change p53 expression at 6 h but induced a 15-fold increase in apoptosis in the crypts of the small intestine. This was associated with only a minor reduction in crypt cell proliferation. Higher doses of MTX increased p53 expression and caused a lower (7-fold) but more prolonged peak of apoptosis that was accompanied by reduced villous area, shortened crypts and a more profound reduction in crypt cell proliferation. Unlike the small intestine, apoptosis in the colon was 10-fold lower, proportional to the dose of MTX and did not induce overt damage. Expression of p21 did not change with any dose at either timepoint. We conclude that apoptosis is not always associated with crypt cell hypoproliferation and that the small intestine can recover after low dose MTX despite a heightened peak of apoptosis of crypt cells. |
Keywords: | Intestine, Small Animals Rats Methotrexate Apoptosis Cell Proliferation Gene Expression Dose-Response Relationship, Drug Female Tumor Suppressor Protein p53 |
Description: | The original publication can be found at www.springerlink.com |
DOI: | 10.1007/s10238-004-0055-y |
Published version: | http://www.springerlink.com/content/x3mj7675kn364278/?p=ea4806217a2f423993459bf9f18956aa&pi=0 |
Appears in Collections: | Aurora harvest 2 Medicine publications |
Files in This Item:
There are no files associated with this item.
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.