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 Table of Contents  
Year : 2016  |  Volume : 7  |  Issue : 3  |  Page : 69-70

Nontargeted effects of radiation: Time to explore the other half of the truth

Radiation Biology and Health Sciences Division, Bhabha Atomic Research Centre, Mumbai, Maharashtra, India

Date of Web Publication10-Jan-2017

Correspondence Address:
Badri N Pandey
Radiation Biology and Health Sciences Division, Bhabha Atomic Research Centre, Mumbai, Maharashtra
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/0973-0168.197972

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How to cite this article:
Pandey BN. Nontargeted effects of radiation: Time to explore the other half of the truth. J Radiat Cancer Res 2016;7:69-70

How to cite this URL:
Pandey BN. Nontargeted effects of radiation: Time to explore the other half of the truth. J Radiat Cancer Res [serial online] 2016 [cited 2021 Nov 30];7:69-70. Available from:

Direct radiation effects are more visible and hence believed to contribute higher to the radiation consequences. However, the manifestation of substantial effects also in the nontargeted cells has resulted in a paradigm shift, which favored the school of thought believing in existence of a bigger biological penumbra than the radiation field. [1] It compelled the radiation biologists to accept the "integrated radiation response" not only at up to tissue but also at the organism level. The nontargeted radiation effects (NTRE) can span widely over the nearby cells (bystander) to the tissues/organs located distantly (abscopal effects). In the early years of 20 th century, the serum clastogenic factors generated after total body irradiation supported the abscopal effect. These studies showed morphological changes in the lymphoid cells cultured in the serum obtained from the animals exposed to radiation. [2],[3] Later on, clastogenic effects were also found in the cancer radiotherapy patients [4] and radiation workers of the Chernobyl accident. [5] Even though bystander signaling is localized at the cellular/tissue level, it holds significant implications in acute and long-term health effects of radiation. Till now, NTRE is by and large ignored, but now with strong evidence generated especially in in vivo models, "radiation biology" cannot be imagined without these effects. Most of the early studies pertaining to NTRE highlighted only its damaging and unidirectional (from irradiated to bystander) face without knowing the truth of masked other half. In this direction, the rescuing [6] and bidirectional NTRE is emerging in literature about radiation protection [7],[8] and cancer radiotherapy. [9] The rescue effect between irradiated and bystander (unirradiated) zebrafish embryo cells was described, which followed nuclear factor κB signaling. [7] Our study using co-culture of human lung carcinoma and counterpart fibroblasts showed transmission of damaging signals from proton microbeam-irradiated lung cancer cells to lung fibroblasts. The rescuing signal generated from bystander fibroblasts protected the irradiated cancer cells against the DNA damage. [9] The role of irradiated stroma in promotion of unirradiated mammary carcinogenesis has been studied after low linear energy transfer and high atomic number/energy radiation. [10],[11] Furthermore, the contribution of unirradiated stroma cells in radiation risk needs to be explored in depth, which will dust off the mirror to show the other side of NTRE signaling in radiation carcinogenesis. In realistic sense, it may be difficult to imagine the cruel or kind face of the other half of NTRE. However, due to expected homeostatic inertia, radiation biologists will be more inclined toward the beneficial NTRE, especially in healthy organism/tissue. An integrated tissue response surrounding a particular irradiated cell would make its best effort to save the damaged cell while inducing their self-protective mechanisms. It may be wisely speculated that the majority of tissue and whole organism remains healthy after radiation stress involving such mechanisms and will tend to keep the organism remain healthy after radiation stress. The situation may be quite different in radiotherapy of cancer where nontargeted effects of radiation to bystander normal and cancer cells are expected to be different depending on whether the bystander counterpart is cancerous or normal. Such hypothesis gets supported by the observation of missing damaging bystander signals from proton-irradiated lung cancer cells to the counterpart normal lung fibroblasts. [9] Such observations suggest a poor possibility of second cancer associated with bystander signaling during cancer radiotherapy, but it may be too early to conclude. The clinical outcome of such effects under cancer radiotherapy scenario will be governed by whether the effect is from cancer to normal or normal to cancer, and that too on whether the nature of the damage is damaging or protective. On the other hand, when the nontargeted cells rescue the irradiated cells in a healthy issue environment, it will minimize the radiation risk. Living systems under homeostasis are dynamic in terms of communication of signals from irradiated to bystander cells or vice versa under normal physiological or stress conditions such as radiation. This makes the "out of box" radiation signaling rather more complicated but exciting. It is hoped that more realistic pictures of NTRE would appear in coming days to unmask the other half of truth to complete the picture. Till then, we need to wait whether the finished image of NTRE contributing to the human health will be ugly or beautiful!

  References Top

Pandey BN. Drift from DNA-centric radiation targets: A paradigm shift in radiation biology. Indian J Radiat Res 2007;4:130-41.  Back to cited text no. 1
Murphy JB, Morton JJ. The lymphocyte as a factor in natural and induced resistance to transplanted cancer. Proc Natl Acad Sci U S A 1915;1:435-7.  Back to cited text no. 2
Murphy JB, Morton JJ. The lymphocyte in natural and induced resistance to transplanted cancer: II. Studies in lymphoid activity. J Exp Med 1915;22:204-11.  Back to cited text no. 3
Parsons WB Jr., Watkins CH, Pease GL, Childs DS Jr. Changes in sternal marrow following roentgen-ray therapy to the spleen in chronic granulocytic leukemia. Cancer 1954;7:179-89.  Back to cited text no. 4
Emerit I, Oganesian N, Sarkisian T, Arutyunyan R, Pogosian A, Asrian K, et al. Clastogenic factors in the plasma of Chernobyl accident recovery workers: Anticlastogenic effect of Ginkgo biloba extract. Radiat Res 1995;144:198-205.  Back to cited text no. 5
Chen S, Zhao Y, Han W, Chiu SK, Zhu L, Wu L, et al. Rescue effects in radiobiology: Unirradiated bystander cells assist irradiated cells through intercellular signal feedback. Mutat Res 2011;706:59-64.  Back to cited text no. 6
Lam RK, Fung YK, Han W, Yu KN. Rescue effects: Irradiated cells helped by unirradiated bystander cells. Int J Mol Sci 2015;16:2591-609.  Back to cited text no. 7
Lam RK, Han W, Yu KN. Unirradiated cells rescue cells exposed to ionizing radiation: Activation of NF-kB pathway in irradiated cells. Mutat Res 2015;782:23-33.  Back to cited text no. 8
Desai S, Kobayashi A, Konishi T, Oikawa M, Pandey BN. Damaging and protective bystander cross-talk between human lung cancer and normal cells after proton microbeam irradiation. Mutat Res 2014;763-764:39-44.  Back to cited text no. 9
Barcellos-Hoff MH, Mao JH. HZE radiation non-targeted effects on the microenvironment that mediate mammary carcinogenesis. Front Oncol 2016;6:57.  Back to cited text no. 10
Barcellos-Hoff MH, Nguyen DH. Radiation carcinogenesis in context: How do irradiated tissues become tumors? Health Phys 2009;97:446-57.  Back to cited text no. 11


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