Low Dose Radiation
Either by targeted effects on irradiated cells or bystander effects on un-irradiated cells, biological effects from low-dose irradiation do occur. What remains controversial is the nature of these effects. On the one hand, mutations and chromosomal aberrations are a proven consequence of low-dose radiation. On the other hand, both bystander cells as well as irradiated cells enjoy increased resistance to subsequent radiation exposure, likely induced by adaptive changes in gene expression induced by direct irradiation and bystander signaling.
Why is the effort to solve these basic issues essential? We live in a world surrounded by potential sources of low-dose radiation exposure. Over the course of our lives, we will encounter these sources knowingly, as with diagnostic X-rays, CT scans, scatter from radiation therapy, or new radiation-based airport scanners; or unknowingly from natural sources such as radon or even a so-called “dirty bomb”. Deciphering the biological effects of low-dose radiation, good or bad, must remain a top research priority because of its profound implications on public health policy and practice. Also, the biological response to environmental toxins is likely to be well conserved, so that lessons from radiobiology will be applicable in many other areas.
We believe that the JBL Center must take the intellectual lead in low-dose radiation research on the molecular, cellular and organismal levels. The results will be of great impact in a number of different areas. First, they will inform us about basic biological mechanisms of stress resistance, intra- and intercellular communication, and adaptation to future stressors. Second, they will answer basic questions about interaction between our genes and the environment. For example, what genes are involved in sensitivity or resistance to low-dose radiation? Does our lifestyle or what we eat prior to exposure affect biological outcomes? Third, the results will inform on current clinical practices using low-dose radiation, for example whether repeated CT scans are safe and how to deal with accidental overexposures that unfortunately are known to occur. Finally, the results may have profound effects on regulatory bodies that set exposure limits. Currently, radiation risk is calculated by linear extrapolation of deleterious effects from high doses to low doses, with the assumption that any and all biological effects are detrimental. Replacing such assumptions with evidenced-based research supported by the JBL Center could profoundly alter the regulatory environment and associated costs to government and private business.
Dr. Little’s cumulative research on both “targeted” and “non-targeted” effects of radiation has been transformative in the field of radiobiology. Today a great deal is known about the cellular response to “targeted” DNA damage, including relevant DNA repair pathways and signaling mechanisms executing cell death or survival programs in response to radiation. It is also known that DNA is not the only target, as irradiating the cytoplasm outside of the nucleus can also lead to radiation-induced genome instability.
Much less is known about cellular homeostatic mechanisms governing stress resistance and how they participate in adaptation to future stressors, particularly in the setting of chronic low-dose stress. Furthermore, the role of the immune system in response to radiation damage is poorly understood, as it can participate both in protection from tumorigenesis through immune surveillance, but also contribute to an inflammatory, tumor-promoting environment. Finally, while it is clear that energy metabolism is intricately linked to stress resistance and declines with age, we still do not understand how these processes are interconnected or how they can be manipulated with diet.