Low-dose ionizing radiations leave scars on human hematopoietic stem and progenitor cells: the role of reactive oxygen species

摘要

After R?ntgen's discovery in 1895, an X-ray became a game changer in medicine.~(~(1)) It was discovered as an invisible ray of light that passes through many objects, including human bodies, and visualizes the internal organs and structures as silhouettes. As now seen in medical radiography, such as chest X-rays and computed tomography (CT) scans, ionizing radiation (IR) has enabled investigation of deep tissues in humans that had been otherwise impossible without surgical intervention, contributing to the early detection and treatment of many diseases. However, as is often the case with new medicine, were shown to have a biohazard effect.~(~(2)) They are identified as a type of IR: a stream of high energy photons that are strong enough to ionize atoms and disrupt molecular bonds in biomolecules, including DNA. As DNA encodes an essential blueprint of a cell, the DNA-damaging property of IR can be toxic. This effect, although used for killing cancer cells in radiotherapy, has raised concerns about the effect of IR on normal tissues and whether the benefits exceed the risks.Modern medicine relies heavily on radiography to assess human health. The annual doses of IR people receive are increasing. A recent study estimated that around 2% or 4,000,000 of the non-elderly adults in the US receive 20 milligray (mGy) or more per year due to medical requirements.~(~(3)) Historically, risks associated with low-dose IR are considered to be almost negligible as it does not cause any acute toxicity, nor does it increase the risk of carcinogenesis, based on empirical linear fits of existing human data determined at high doses, such as those of Japanese atomic bomb survivors. ~(~(4)) Indeed, low-dose IR rarely induces DNA double strand breaks (DSB), which often cause mutations and are considered to be the most relevant lesion for the deleterious effects of IR.~(~(5)) However, even though low-dose IR rarely cause DSB, they are reportedly less easy to repair than those induced by high-dose IR .~(~(6)) Importantly, recent evidence suggests that cumulative doses of 50 mGy IR (doses equivalent to 5-10 brain CT scans when given in childhood) have longterm detrimental effects on human health, including a more than 3-fold increase in the risks of acute lymphoblastic leukemia and myelodysplastic syndrome.~(~(7)) Furthermore, mouse studies demonstrate that low-dose IR affect function of long-lived tissue-specific stem cells, including hematopoietic stem cells (HSC).~(~(8),~(9)) Thus, understanding the persistent effect of low-dose IR on human tissue-specific stem cells is of particular importance in precisely evaluating the risks posed by radiography on public health.