Differential toxicity of radiation with different dose-rates between testis and bone marrow cells via the differential regulation of ROS, Ca2+, and mitochondria membrane potential

Abstract

It is believed that there may be a proportional relationship between the dose-rate and adverse effects of radiation for a given dose. However, we have previously shown that low dose-rate (LDR) radiation induces greater toxicity in the testes than that induced by high-dose rate (HDR) radiation, in contrast to results for the thymic lymphoma induction rate. Since cell/organ toxicity and cancer induction rates may not be directly comparable, we compared toxicities following LDR and HDR radiation between testis/spermatogenesis and bone marrow/hematopoiesis, similar organs/cells in terms of continuously producing progenitor cells. The two organs showed opposite patterns of toxicity due to LDR and HDR radiation, supporting the differential dose-rate effect between the two organs. Furthermore, reactive oxygen species (ROS), Ca²⁺ and mitochondria membrane potential (MMP) were specifically regulated between the two organs by LDR and HDR. These results suggest that LDR radiation may enhance toxicity specifically in the testes but not in the bone marrow via the specific regulation of ROS, Ca²⁺, and MMP in single testis/spermatogonia. This report provides the evidence that radiation at different dose rates induces differential toxicity depending on the organ, accompanied by the differential regulation of key cellular parameters, such as ROS, Ca²⁺ and MMP.