Radiation-induced apoptosis and gene expression in neonatal kidney and testis with and without protein synthesis inhibition

Gobe, G. C., Harmon, B., Leighton, J. and Allan, D. J. (1999) Radiation-induced apoptosis and gene expression in neonatal kidney and testis with and without protein synthesis inhibition. International Journal of Radiation Biology, 75 8: 973-983. doi:10.1080/095530099139737

Author Gobe, G. C.
Harmon, B.
Leighton, J.
Allan, D. J.
Title Radiation-induced apoptosis and gene expression in neonatal kidney and testis with and without protein synthesis inhibition
Journal name International Journal of Radiation Biology   Check publisher's open access policy
ISSN 0955-3002
Publication date 1999
Sub-type Article (original research)
DOI 10.1080/095530099139737
Volume 75
Issue 8
Start page 973
End page 983
Total pages 11
Place of publication London, England
Publisher Taylor & Francis
Collection year 1999
Language eng
Subject C1
321020 Pathology
730115 Urogenital system and disorders
Abstract Purpose: To analyse the incidence of radiation-induced apoptosis, expression of two apoptosis-related genes, Bcl-2 and p53, and post-radiation levels of cell proliferation in the neonatal rat (4-5 days old) kidney and testis. Materials and methods: Apoptosis was quantified in control or treated kidney or testis at 2, 4, 6, 8 and 24 h after 5 Gy of whole body X-irradiation (n = 4 per group). Morphology (light and electron microscopy) and DNA gel electrophoresis were used to assess apoptosis. Temporal and spatial expression of Bcl-2 or p53 were analysed using immunohistochemistry. Administration of cycloheximide (1.5 mg/kg) was used to determine whether new protein synthesis had a role in induction of apoptosis. Tritiated thymidine uptake and autoradiography were used to indicate alterations in cell proliferation (radiolabel administered Ih prior to tissue collection) or S-phase cells undergoing radiation-induced apoptosis (radiolabel administered Ih prior to irradiation). Results: Apoptosis peaked at 4 h in the testis and 6 h in the kidney and was significantly higher in the renal nephrogenic zone than in the testis (p < 0.05). Mitosis was almost completely negated after irradiation in both tissues. A higher proportion (almost fivefold) of the apoptotic cells died in S phase in the kidney than in the testis. Cycloheximide negated induction of apoptosis in the kidney, and markedly decreased apoptosis in the testis. Bcl-2 expression was highest in the differentiated zone of control kidneys and increased after irradiation in the nephrogenic zone, particularly near foci of apoptosis in developing nephrons. In the control testis, Sertoli cells had moderate expression of Bcl-2. After irradiation, there was complete absence of Bcl-2 expression in apoptotic Sertoli cells, with surviving cells increasing Bcl-2 expression. Irradiated kidney had more intense nuclear p53 expression compared with controls. In the testis, p53 that was present in controls continued to be expressed in surviving cells but not apoptotic cells in radiation-treated animals. Conclusions: Unique differences can be identified between the incidence and biomolecular control of radiation-induced apoptosis in the normal neonatal kidney and testis. These results may find application for minimizing damage to these normal neonatal tissues in the development of, for example, cancer treatment regimens.
Keyword Biology
Nuclear Science & Technology
Radiology, Nuclear Medicine & Medical Imaging
Barr-virus Infection
Induced Cell-death
Cancer Cells
Q-Index Code C1

Document type: Journal Article
Sub-type: Article (original research)
Collection: School of Medicine Publications
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Citation counts: TR Web of Science Citation Count  Cited 13 times in Thomson Reuters Web of Science Article | Citations
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Created: Tue, 10 Jun 2008, 13:50:39 EST