Role of cell cycle control in radiosensitization of mouse spermatogonial stem cells.
OBJECTIVE
To investigate the possible role of cell cycle arrest in the radiosensitization of mouse spermatogonial stem cells due to small conditioning X-ray exposures.


METHODS
A 24 h fractionation interval between conditioning (1 Gy) 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 posttreatment 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.
Department of Radiation Genetics and Chemical Mutagenesis-MGC, Leiden University Medical Center, The Netherlands. Hp.p.w.-vanbuul@lumc.nl
P P
PP
Van Buul
A
A
Van Duyn-Goedhart
T
T
Beumer
A L
AL
Bootsma
D000818:Animals; D001549:Benzamides / Q000494:pharmacology; D002110:Caffeine / Q000494:pharmacology; D002453:Cell Cycle / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects*; D019583:Dose Fractionation, Radiation; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D011836:Radiation Tolerance / Q000187:drug effects / Q000528:radiation effects*; D011838:Radiation-Sensitizing Agents / Q000494:pharmacology; D013093:Spermatogonia / Q000166:cytology / Q000187:drug effects / Q000528:radiation effects*; D013234:Stem Cells / Q000166:cytology / Q000187:drug effects / Q000528:radiation effects*; D016159:Tumor Suppressor Protein p53 / Q000172:deficiency / Q000235:genetics
D001549:Benzamides; D010726:Phosphodiesterase Inhibitors; D011838:Radiation-Sensitizing Agents; D016159:Tumor Suppressor Protein p53; D002110:Caffeine; C025160:3-aminobenzamide