Biological basis of radiation protection needs rejuvenation

Abstract

Purpose: Human beings encounter radiation in many different situations - from proximity to radioactive waste sites to participation in medical procedures using X-rays etc. Limits for radiation exposures are legally regulated; however, current radiation protection policy does not explicitly acknowledge that biological, cellular and molecular effects of low doses and low dose rates of radiation differ from effects induced by medium and high dose radiation exposures. Recent technical developments in biology and medicine, from single cell techniques to big data computational research, have enabled new approaches for study of biology of low doses of radiation. Results of the work done so far support the idea that low doses of radiation have effects that differ from those associated with high dose exposures; this work, however, is far from sufficient for the development of a new theoretical framework needed for the understanding of low dose radiation exposures.

Conclusions: Mechanistic understanding of radiation effects at low doses is necessary in order to develop better radiation protection policy.

Keywords: Biological effects of ionizing radiation; low dose radiation; radiation protection.

Figure 1.

Life-shortening data from mice exposed to acute and protracted radiation up to 1.5 Gy total dose, following BEIR VII procedure (for more details see Haley et al. 2015); currently used model based on linear-quadratic formula and alternative linear-linear model comparisons. Comparison of predicted life-shortening from protracted radiation exposures in a 0–1.5 Gy total dose range when only acute animal irradiation data on life-shortening is used to calculate DDREF (dotted red line) vs. when both acute and protracted data are compared (full lines) (a). In both cases calculations are based on BEIR VII approach, however, in one case (dotted red line) the graph is based on acute exposures, similar to extrapolations done from A-bomb survivor data. In the other case, calculation is done considering both acute and protracted dose exposures, and the graph of life-shortening associated with protracted exposures is shown by a full red line. Moreover, a simpler liner-linear model provides a better fit with the data than the currently used linear-quadratic model. The Akaike Information Criteria (AIC) estimates appear above each fit and quantify the goodness of fit: a lower value indicates a better fit. Overall AIC value for linear-quadratic model (−749) (b) is greater than the AIC value for liner-linear model (−765) (c), indicating that the linear-linear model fits the data better.

Figure 2.

DDREF calculations for cancer risk with increased dose of radiation up to 2 Gy done by BEIR VII based on animal cancer data should be reconsidered. Top panels - original BEIR VII graphs include a mix of leukemia and solid cancers as well as a mix of lethal and non-lethal cancers. A DDREF calculation was done for these data summarily leading to the calculated DDREF value of 1.3. Bottom panels depict the same graphs but only for solid cancers, and exclude non-lethal cancers such as Harderian gland cancer. Moreover, lung cancer data used by BEIR VII includes some benign pulmonary adenomas. If these more limited data were used, the DDREF calculation outcome would be different. In other words, DDREF recalculation requires careful data pruning and direct comparisons for acute and protracted data as it was done for life-shortening in Figure 1.

Figure 3.

Progress in molecular biology over the past 20 years focusing on nucleic acids and proteins and their modifications.