Role of cell cycle control in radiosensitization of mouse spermatogonial stem cells

• Published in: International journal of radiation biology Vol. 77; no. 3; pp. 357 - 363
• Main Authors: Van Buul, P. P. W., Van Duyn-Goedhart, A., Beumer, T., Bootsma, A. L.
• Format: Journal Article
• Language: English
• Published: London Informa UK Ltd 2001; Taylor & Francis
• Subjects: Animals; Benzamides - pharmacology; Biological and medical sciences; Biological effects of radiation; Caffeine - pharmacology; Cell Cycle - drug effects; Cell Cycle - physiology; Cell Cycle - radiation effects; Dose Fractionation, Radiation; Fundamental and applied biological sciences. Psychology; Hormone metabolism and regulation; Ionizing radiations; Male; Mammalian male genital system; Mice; Mice, Inbred C57BL; Mice, Knockout; Phosphodiesterase Inhibitors - pharmacology; Radiation Tolerance - drug effects; Radiation Tolerance - radiation effects; Radiation-Sensitizing Agents - pharmacology; Spermatogonia - cytology; Spermatogonia - drug effects; Spermatogonia - radiation effects; Stem Cells - cytology; Stem Cells - drug effects; Stem Cells - radiation effects; Tissues, organs and organisms biophysics; Tumor Suppressor Protein p53 - deficiency; Tumor Suppressor Protein p53 - genetics; Vertebrates: reproduction; Evaluation; Animal model; Radiosensitivity; Pathophysiology; Stem cell; Rodentia; Male; Experimental study; X ray irradiation; Vertebrata; Ionizing irradiation; Mammalia; TP53 Gene; Mouse; Animal; Spermatogonia; Cell cycle; Survival curve
• ISSN: 0955-3002; 1362-3095
• DOI: 10.1080/09553000010009035

Purpose : To investigate the possible role of cell cycle arrest in the radiosensitization of mouse spermatogonial stem cells due to small conditioning X-ray exposures. Materials and methods : A 24 h fractionation interval between conditioning (1Gy) and challenging (8 or 9 Gy) exposures was used. Two approaches were followed: the first in the Swiss random-bred wild-type mouse of the radiation-induced cell cycle arrest-evading agents 3-aminobenzamide (3-AB) and caffeine; and, second, using the C57BL/6 mouse of different p53 status. As biological parameter stem cell survival was analysed by the repopulation index (RI) method and chromosomal translocations were recorded using spermatocyte analysis at appropriate post-treatment periods. Results : In the Swiss wild-type mouse, the application of 3-AB or caffeine significantly suppressed the sensitization of stem cells towards killing or translocation induction. In the C57BL/6 mouse, somewhat more variability in response was observed but no significant differences in sensitization between the p53+/+, +/- or -/- mouse were recorded, suggesting no involvement of p53 in this process. Conclusions : The results indicate that p53-independent cell cycle regulation plays an important role in the radiosensitization of mouse spermatogonial stem cells.