Differential effects of ionizing radiation and platinum-derivative chemotherapy on apoptotic pathways in testicular germ cells.

Purpose: The purpose here was to identify whether ionizing radiation and oxaliplatin triggered testicular germ cells apoptosis through different executionary pathways.
Materials and Methods: Adult male mice are treated with oxaliplatin (0.5 mg/kg, Ox) 4 h before being locally irradiated (0.5 Gy, IR, considered as time 0 h).
Results: The number of apoptotic germ cells was significantly higher for IR (p < 0.008), Ox (p < 0.0001) and Ox + IR (p < 0.0001) groups compared to the untreated mice group. Similarly, the different treatments induced an increase of p53 expression. Downstream p53, IR and Ox used different pathways. Indeed, IR increased effector caspase-3 expression in terms of mRNA (p < 0.002), pro-enzyme p < 0.0001) and active (3.7-fold, p < 0.003) protein levels but not the inhibitors of apoptosis proteins (IAP) including cIAP1, cIAP2 and XIAP. In contrast, while oxaliplatin treatment had no apparent effect on caspase-3 expression, it significantly decreased the cIAP1 (p < 0.005), cIAP2 (p < 0.008) and XIAP (p < 0.02) proteins levels. Finally, the combination of both treatments decreased IAP expression but did not modify caspase-3 levels while it increased the AIF (apoptosis-inducing factor) protein levels (5.5-fold, p < 0.003). No modification of AIF levels was observed with OX or IR alone.
Conclusions: Together, these results indicate that the platinum analogue oxaliplatin and the ionizing radiations trigger apoptosis in the testicular germ cells, probably through different pathways.