Adaptive Response in Embryogenesis: V. Existence of Two Efficient Dose-Rate Ranges for 0.3 Gy of Priming Irradiation to Adapt Mouse Fetuses

Abstract

The adaptive response is an important phenomenon in radiobiology. A study of the conditions essential for the induction of an adaptive response is of critical importance to understanding the novel biological defense mechanisms against the hazardous effects of radiation. In our previous studies, the specific dose and timing of radiation for induction of an adaptive response were studied in ICR mouse fetuses. We found that exposure of the fetuses on embryonic day 11 to a priming dose of 0.3 Gy significantly suppressed prenatal death and malformation induced by a challenging dose of radiation on embryonic day 12. Since a significant dose-rate effect has been observed in a variety of radiobiological phenomena, the effect of dose rate on the effectiveness of induction of an adaptive response by a priming dose of 0.3 Gy administered to fetuses on embryonic day 11 was investigated over the range from 0.06 to 5.0 Gy/min. The occurrence of apoptosis in limb buds, incidences of prenatal death and digital defects, and postnatal mortality induced by a challenging dose of 3.5 Gy given at 1.8 Gy/min to the fetuses on embryonic day 12 were the biological end points examined. Unexpectedly, effective induction of an adaptive response was observed within two dose-rate ranges for the same dose of priming radiation, from 0.18 to 0.98 Gy/ min and from 3.5 to 4.6 Gy/min, for reduction of the detrimental effect induced by a challenging dose of 3.5 Gy. In contrast, when the priming irradiation was delivered at a dose rate outside these two ranges, no protective effect was observed, and at some dose rates elevation of detrimental effects was observed. In general, neither a normal nor a reverse dose- rate effect was found in the dose-rate range tested. These results clearly indicated that the dose rate at which the priming irradiation was delivered played a crucial role in the induction of an adaptive response. This paper provides the first evidence for the existence of two dose-rate ranges for the same dose of priming radiation to successfully induce an adaptive response in mouse fetuses.

Adaptive Response of Low Linear Energy Transfer X‐rays for Protection Against High Linear Energy Transfer Accelerated Heavy Ion‐Induced Teratogenesis

“…Later AR in utero was verified and confirmed in different laboratories (Mitchel et al., ; Okazaki et al., ). In a series of investigations during characterization of our AR fetal mouse model, results are accumulating that (1) there exist efficient doses and dose rates for delivery of the priming irradiations, (2) Trp53 is essential for AR induction, (3) reduction of prenatal death and malformation is due to inhibition of radiation‐induced Trp53‐dependent apoptosis, (4) signal transduction and Trp53‐related pathways are involved in the AR induction, (5) phosphorylation of Trp53 protein is responsible for inhibition of radiation‐induced Trp53‐dependent apoptosis (Wang et al., ; Wang et al., ; Wang et al., ; Wang et al., ; Wang et al., ; Varès et al., ; Varès et al., ). These data obtained so far indicate that AR in fetal mice is a complicated phenomenon resulted from the interplay among the animal (strain and developmental stage), radiation (dose and dose rate), and timing for delivery of irradiations (interval between the priming dose and the challenge dose).…”

Low dose gamma-irradiation differentially modulates antioxidant defense in liver and lungs of Balb/c mice

“…Generally, damaging or lethal cellular effects are observed following high radiation doses (Cuttler & Pollycove 2003), while cellular stimulatory effects are observed following low-dose-short-term exposures in the range 0.01 -0.50 Gy (1 -50 rad). These stimulatory effects include adaptive responses (Shadley et al 1987, Sankaranarayanan et al 1989, Wang et al 1991, Ikushima et al 1996, Wang et al 2004 ), activation of immune functions (Liu et al 1987, James & Makinodan 1988, Safwat 2000, Ibuki & Goto 2004, Ina & Sakai 2004, Kojima et al 2004, Ina et al 2005, stimulation of growth (Luckey 1982), enhancement of resistance to high-dose radiation (Yonezawa et al 1990(Yonezawa et al , 1996, prevention of brain disorders (Ibuki & Goto 1994), and an increase in the life span of mice (Tiku & Kale 2004). This phenomenon of beneficial biological effects of low-dose radiation has generally been termed as 'radiation hormesis', and little is known about its mechanism(s).…”

Immunohistochemical Study of Postnatal Neurogenesis After Whole-body Exposure to Electromagnetic Fields: Evaluation of Age- and Dose-Related Changes in Rats

“…cells within the RMS after long-term EMF exposure, both applied at P7 rats, show the boundary between non-genotoxic and genotoxic doses of irradiation. Irradiation, as a genotoxic agent, activates the cell-cycle checkpoint and results in temporary cell growth arrest, which allows DNA repair before proliferation or induces cell apoptosis (Erenpreisa and Cragg 2001;Uberti et al 2001;Wang et al 2004). Our data suggest that due to the cumulative effect of 3 days (8 h/day) of irradiation, surviving stem cells are unable to regenerate and migrate even after 3 weeks postirradiation so we consider the dose as genotoxic.…”