Document Detail


Differential expression of growth factors in irradiated mouse testes.
MedLine Citation:
PMID:  11316565     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
PURPOSE: By using as an experimental model the male mouse gonad, which contains both radiosensitive (germ) and radioresistant (somatic) cells, we have studied the growth factor (and/or receptor) expression of transforming growth factor-beta receptor (TGFbeta RI), stem cell factor (SCF), c-kit, Fas-L, Fas, tumor necrosis factor receptor (TNF R55), and leukemia inhibiting factor receptor (LIF-R) after local irradiation. METHODS AND MATERIALS: Adult male mice were locally irradiated on the testes. Induction of apoptosis in the different testicular cell types following X-ray radiation was identified by the TdT-mediated dUTP Nick End Labeling (TUNEL) approach. Growth factor expression was evidenced by semiquantitative RT-PCR and Western blot analyses. RESULTS: Apoptosis, identified through the TUNEL approach, occurred in radiosensitive testicular (premeotic) germ cells with the following kinetics: the number of apoptotic cells increased after 24 h (p < 0.001) and was maximal 48 h after a 2-Gy ionizing radiation (p < 0.001). Apoptotic cells were no longer observed 72 h after a 2-Gy irradiation. The number of apoptotic cells increased with the dose of irradiation (1-4 Gy). In the seminiferous tubules, the growth factor expression in premeiotic radiosensitive germ cells was modulated by irradiation. Indeed Fas, c-kit, and LIF-R expression, which occurs in (radiosensitive) germ cells, decreased 24 h after a 2-Gy irradiation, and the maximal decrease was observed with a 4-Gy irradiation. The decrease in Stra8 expression occurred earlier, at 4 h after a 2-Gy irradiation. In addition, a significant (p < 0.03) decrease in Stra8 mRNA levels was observed at the lowest dose used (0.5 Gy, 48 h). Moreover, concerning a growth factor receptor, such as TGFbeta RI, which is expressed both in radiosensitive and radioresistant cells, we observed a differential expression depending on the cell radiosensitivity after irradiation. Indeed, TGFbeta RI expression was increased after irradiation in interstitial radioresistant testicular cells in a dose- and time-dependent manner, while it decreased in seminiferous radiosensitive (germ cells) testicular cells. Such a differential expression between radioresistant and radiosensitive cells in TGFbeta RI levels was observed in terms of both mRNA and protein. In contrast, the growth factors specifically expressed in the somatic radioresistant (Sertoli) cells in the seminiferous tubules (SCF, Fas-L, TNF R55) were not affected by ionizing radiation (up to 4 Gy, 72 h). CONCLUSION: Growth factor expression decreased in the radiosensitive testicular cells after irradiation. Such a decrease occurred before the detection of apoptosis using the TUNEL approach. TGFbeta RI mRNA levels decreased in the radiosensitive cells, whereas it increased in the radioresistant cells, suggesting that TGFbeta RI may represent a biomarker of the intrinsic radiosensitivity of cells.
Authors:
C Mauduit; A Siah; M Foch; O Chapet; S Clippe; J P Gerard; M Benahmed
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  International journal of radiation oncology, biology, physics     Volume:  50     ISSN:  0360-3016     ISO Abbreviation:  Int. J. Radiat. Oncol. Biol. Phys.     Publication Date:  2001 May 
Date Detail:
Created Date:  2001-04-24     Completed Date:  2001-05-17     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  7603616     Medline TA:  Int J Radiat Oncol Biol Phys     Country:  United States    
Other Details:
Languages:  eng     Pagination:  203-12     Citation Subset:  IM    
Affiliation:
Laboratoire de Recherche sur les Communications Cellulaires en Biologie de la Reproduction, Institut National de la Santé et de la Recherche Médicale, Faculté de Médecine Lyon-Sud, BP 12, 69 921 Oullins cedex, France. mauduit@lsgrisn1.univ-lyon1.fr
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MeSH Terms
Descriptor/Qualifier:
Animals
Apoptosis / radiation effects
Growth Substances / biosynthesis*
Male
Mice
Radiation Tolerance / physiology
Receptors, Growth Factor / biosynthesis
Receptors, Transforming Growth Factor beta / biosynthesis
Reverse Transcriptase Polymerase Chain Reaction
Sertoli Cells / metabolism,  radiation effects
Spermatozoa / metabolism,  radiation effects
Testis / cytology,  metabolism*,  radiation effects*
Chemical
Reg. No./Substance:
0/Growth Substances; 0/Receptors, Growth Factor; 0/Receptors, Transforming Growth Factor beta

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