Rajan and Pandey have recently investigated the effects of low doses of alpha particles on human cancer cells. These researchers observed that in contrast to the tumoricidal effects seen at high doses, human lung adenocarcinoma (A549) cells irradiated with low doses of alpha radiation were more proliferative and tumor volume increased both in vitro and in vivo. The results derived from the paper authored by Rajan and Pandey pose a number of interesting questions.
Rajan and Pandey did not focus sufficient attention on other key applications of their findings in radiobiology and radiotherapy. For example, a key question is whether we can conclude that patients with lung adenocarcinoma should decrease their indoor radon levels. Although we have tried to answer this question in our LTE, I believe there is still room for exploring different aspects of the findings of these researchers.
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The observation of low dose stimulated proliferation of A549 cells and NCI-H292 cells would be interesting indeed. A significant proliferation was observed at 1.36 cGy and 6.1 cGy, but not at 0.68 cGy, suggesting that such a sensitive dose range is narrow. This is somewhat reminiscent of the earlier observation that 2–5 cGy of X-rays stimulates proliferation of normal human fibroblasts ( https://pubmed.ncbi.nlm.nih.gov/11454682/ ).
Dose rate (particle fluence) in this experiment was 1.36 cGy/min, which is much higher that that of residential radon. At lower fluence of high-LET particles, bystander cell killing may occur, as reported in A549 cells. Article Heavy-ion-induced bystander killing of human lung cancer cel...
Nobuyuki Hamada Thank you so much for your insightful comments. Regarding the dose range, you're right. It has long been known that there's a window of dose and dose rate for hormetic responses. This window not only varies in different species but within a specific species. As you mentioned, in some cases, the window is very narrow. This is the reason that many studies failed to show any hormetic effects at low doses.
Nobuyuki Hamada Another point that in my opinion, needs careful attention is the "negative hormesis" that is observed as the stimulated proliferation of A549 cells after exposure to LDR. Current data on this point is limited and further studies are needed.
My pleasure, Prof. SMJ Mortazavi . Radiation-induced cell proliferation has been reported at various dose levels. Article Ionizing Irradiation Not Only Inactivates Clonogenic Potenti...
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Nobuyuki Hamada Dear Dr. Hamada thank you very much for sharing your papers.
Nobuyuki Hamada I highly appreciate your opinion about the following questions:
1. Is Low-Dose Radiation-Induced Cell Proliferation in Cancer Cells a common phenomenon?
2. If it's not so common, which factors may trigger such a response?
At various dose levels, Radiation-induced cell proliferation (in contrast to radiation-induced cell killing) occurs in irradiated normal and cancer cells, bystander-induced cell proliferation occurring in their bystander cells. The following paper ( https://pubmed.ncbi.nlm.nih.gov/10728689/ ) is an example bystander-induced proliferation of normal lung cells.
Such stimulated proliferation may not necessarily be beneficial to the tissue or organs. Cell proliferation after high dose (e.g., >2 Gy of low-LET radiation) may serve as a compensatory mechanism in various tissues (e.g., via stem cell proliferation), but may underlie cataractogenesis in the ocular lens.
Stimulation or suppression of cell proliferation rely on various factors, but the same factor (e.g., growth factors, cytokines, ROS and NO radicals) can play a "pleiotropic" role. For example, TGF-beta is pro-mitogenic for some mesenchymal cells (e.g., fibroblasts), but anti-mitogenic for epithelial, endothelial and hematopoietic cells. TGF-beta can also be pro-mitogenic for adult human
skin fibroblasts, but anti-mitogenic for fetal fibroblasts. Even within the same fetal fibroblast cell line, TGF-beta can be promitogenic at low concentrations, but anti-mitogenic at high concentrations. For details, please see below (references therein).Article Signaling Pathways Underpinning the Manifestations of Ionizi...
You're indeed right but surprisingly, in the experiments performed by Rajan and Pandey, only human lung adenocarcinoma cells irradiated with low doses of alpha radiation were more proliferative and tumor volume increased both in vitro and in vivo. Therefore, it could be hypothesized that patients with lung adenocarcinoma should decrease their indoor radon level. However, we believe that such an action is not needed.
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