The role of dose rate in radiation cancer risk: evaluating the effect of dose rate at the molecular, cellular and tissue levels using key events in critical pathways following exposure to low LET radiation

Abstract

Purpose: This review evaluates the role of dose rate on cell and molecular responses. It focuses on the influence of dose rate on key events in critical pathways in the development of cancer. This approach is similar to that used by the U.S. EPA and others to evaluate risk from chemicals. It provides a mechanistic method to account for the influence of the dose rate from low-LET radiation, especially in the low-dose region on cancer risk assessment. Molecular, cellular, and tissues changes are observed in many key events and change as a function of dose rate. The magnitude and direction of change can be used to help establish an appropriate dose rate effectiveness factor (DREF). Conclusions: Extensive data on key events suggest that exposure to low dose-rates are less effective in producing changes than high dose rates. Most of these data at the molecular and cellular level support a large (2–30) DREF. In addition, some evidence suggests that doses delivered at a low dose rate decrease damage to levels below that observed in the controls. However, there are some data human and mechanistic data that support a dose-rate effectiveness factor of 1. In summary, a review of the available molecular, cellular and tissue data indicates that not only is dose rate an important variable in understanding radiation risk but it also supports the selection of a DREF greater than one as currently recommended by ICRP (2007) and BEIR VII (NRC/NAS 2006).

Genotoxic effects of high dose rate X‐ray and low dose rate gamma radiation in ApcMin/+ mice

“…Previous studies have addressed the influence of gamma dose rate on cancer in mice, demonstrating increased tumorigenic effectiveness of radiation exposure with increased dose rate (Ullrich and Storer, ). Moreover, the influence of dose rate on genotoxic and other endpoints has been extensively reviewed (Brooks et al, ).…”

Effects of mucus thickness and goblet cell hyperplasia on microdosimetric quantities characterizing the bronchial epithelium upon radon exposure

“…There is an on-going debate about the role of dose rate as a modifier of radiation effects (R€ uhm et al 2015;Brooks et al 2016). The present study shows that the effects of acute and chronic exposures can be qualitatively different.…”

Dose-dependency and reversibility of radiation-induced injury in cardiac explant-derived cells of mice

“…Second, radiation exposure was done at a high dose rate (>12 Gy per hour) in our study. As the dose rate has been largely taken into consideration on radiation-induced cancer risk28, it will be of interesting to evaluate the radiation-induced injury in CDCs with a low dose rate exposure (<5 mGy per hour). Third, the reversibility of radiation-induced injury in CDCs was only investigated at 1 and 3 weeks after a single exposure to 3 Gy γ-rays due to the very limited foundation and man-power.…”