Abstract
Radiation-induced abscopal effect (RIAE) may influence radiotherapy efficiency. However, it is unknown whether RIAE triggers abnormal genetic consequence. We present a novel evidence that, when mice were given fractionated irradiation on right thorax, the ultrastructure of blood-testis barrier was damaged in company with apoptosis induction in testes, and the sperm number and vitality were drastically decreased so that both the fertility and the survival of their offspring were reduced. Protein microarray assay and hormone detection showed that some cytokines especially TNF-α, TGF-β and estradiol in the serum of irradiated mice increased to higher levels in consistent with abscopal damage, and this conditioned serum had toxic effect on TM4 cells in vitro. When the mice were fed with cimetidine, the above abscopal responses were significantly attenuated. This study demonstrates in the first time that the thoracic irradiation (Th-IR) induces structural and functional damage in the distal testes and further cause fertility decline of irradiated male mice, which may have important implications in the strategy development of radiotherapy in avoiding abnormal genetic consequence.
Highlights
Radiation-induced abscopal effect (RIAE) may influence radiotherapy efficiency
180 after thoracic irradiation (Th-ionizing radiation (IR)), the arrangement of spermatogenic cells was reorganized to normal status, but the gap between seminiferous tubules was still larger and the number of sperm cells was less than the control group
This study demonstrates for the first time that Th-IR induces distal damage in testes including morphological structure damage, apoptosis induction, sperm validity decreases, and even yields genetic damage of fertility decline
Summary
Radiation-induced abscopal effect (RIAE) may influence radiotherapy efficiency. it is unknown whether RIAE triggers abnormal genetic consequence. This study demonstrates in the first time that the thoracic irradiation (Th-IR) induces structural and functional damage in the distal testes and further cause fertility decline of irradiated male mice, which may have important implications in the strategy development of radiotherapy in avoiding abnormal genetic consequence. Radiotherapy is a main treatment method of lung cancer and it could stimulate acute responses such as inflammation and pneumonitis and even induce chronic effects of pulmonary fibrosis[19]. During this radiotherapy, the normal tissue of lung will be unavoidably irradiated, but so far it is unknown whether this radiation damage could induce any harmful abscopal effects on distal tissues. The potential signaling factors involved in this RIAE are explored
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