Year : 2017 | Volume
: 8 | Issue : 1 | Page : 1--3
Carcinogenic risk from low-dose radiation exposure is overestimated
Kaushala P Mishra
BM International Research Center, Jain Vishwa Bharati Institute (Deemed University), Ladun, Rajasthan; Ex Bhabha Atomic Research Center; Foundation for Education and Research, Mumbai, Maharastra, India
Kaushala P Mishra
BM International Research Center, Jain Vishwa Bharati Institute (Deemed University), Ladun, Rajasthan; Ex Bhabha Atomic Research Center; Foundation for Education and Research, Mumbai, Maharastra
|How to cite this article:|
Mishra KP. Carcinogenic risk from low-dose radiation exposure is overestimated.J Radiat Cancer Res 2017;8:1-3
|How to cite this URL:|
Mishra KP. Carcinogenic risk from low-dose radiation exposure is overestimated. J Radiat Cancer Res [serial online] 2017 [cited 2020 Jun 3 ];8:1-3
Available from: http://www.journalrcr.org/text.asp?2017/8/1/1/199303
Living beings have evolved in the high-intensity ionizing radiation since ancient times. At present, the average annual natural background exposure ranges from 1 to 260 mSv at various places on the earth. Currently estimated annual world average of environmental radiation is 2.4 mSv. It is noteworthy that humans have lived long with varying degrees of exposures to radiation from land, space, and own bodies without any notable health problem. Numerous research studies have failed to detect and document any adverse health effect among people living in various natural background radiation., The ancient radiation-rich history of life implies that extant life forms must have developed adaptive machinery, biologic repair mechanisms, and/or efficient removal of radiation-damaged centers in the body.
It is pertinent to realize that with the discoveries of X-ray by W. Roentgen (1895) and radioactivity by Henry Becquerel (1898), an unusual excitement was generated among scientists as well as general public for their possible use in the treatment of diseases. In the ensuing years, physicians began treating patients and scientists began intensifying their research in laboratories. There was no concern for any harm to health. However, it was recognized within a decade of these practices that those conducting experiments or treating patients suffered from leukemia. Madam Curie who discovered radium and was awarded the Nobel Prize and actively conducted further research was diagnosed with leukemia and succumbed to this disease. In the succeeding years, many other researchers and physicians were diagnosed with cancer, which drew the attention of scientists to harmful effects of ionizing radiation. Subsequently, intensive research began to understand the biological effects of ionizing radiation (BEIR) giving birth to the new discipline of “Radiation Biology.” Research was actively pursued on radiation effects on microorganisms, plants, animals, and populations. Among many mysteries of biological systems, cellular responses to external agents, particularly ionizing radiations, have been unraveled.
In view of the increasing use of radiation science and technology in research, medicine, and nuclear energy sector in the 20th century, the concern of health effects of radiation received growing attention, and the criteria of radiation safety were developed. To regulate the standards for radiation protection and enforce safety procedures, the International Commission for Radiation Protection (ICRP) was formed in 1928. In addition, the US National Academy of Sciences constituted Biological Effects of Atomic Radiation, later renamed as BEIR, to collate research data on radiation-induced cancer (carcinogenesis) and genetic effects, especially hereditary diseases. These scientific bodies have produced their reports based on the results obtained from progress of radiobiological research.
Radiation research community in 1940s investigated the mechanism of radiation-induced cancer in various models. Studies revealed that high doses of radiation transform cells by the process of mutation arising from damage to DNA. Mainly from research on fruit fly, Hermann Muller suggested that radiation causes mutation which followed linearity with dose linear-no-threshold (LNT). In 1946, Hermann Muller in his Nobel Lecture asserted that a no-harm threshold was nonexistent since linearity had been demonstrated for doses down to 4 Gy. It is important to note that there is no credible evidence for validity of carcinogenicity at low doses (<100 mGy) and low dose rates. The LNT hypothesis extrapolation from evidence-supported, high-dose effects to low-dose responses claims that all acute ionizing radiation exposures down to zero are harmful. The harm is proportional to dose and is cumulative throughout life, regardless of how low the dose rate is.
The worldwide radiation protection standards for late (stochastic) effects are based on the LNT hypothesis. However, it has been well established that the typical biophysical dose-effect dependence on the organism is rather nonlinear in the full range of ionizing radiation doses, as reported in many experiments and reviews. Such dependence may have a sigmoidal shape, which has been found in animals as well as in humans. In the experiment, this problem is usually considered with reference to the cancer incidence and mortality, while dose response is often studied on single cell. The general dose-response shape, which is sigmoidal, is shown to be modified by such mechanisms as adaptive response or bystander effect. The many aspects of the sigmoid function most appropriately demonstrate the relationships among irradiated organisms. The sigmoidal function is typically quadratic (parabolic) at low doses, almost linear for medium values, and asymptotically tends toward the maximum at high values. It appears to be an adequate dependence both for deterministic as well as for the stochastic results.
Radiation protection standards are based on LNT principle. This model finds support from Life Span Study of Hiroshima Atomic Bomb Survivors., The analysis of data and interpretations has, however, been improved, and nonapplicability of LNT has been suggested. The assumption of all radiation-induced DNA damages resulting in mutation has been denied in several studies. Therefore, mechanisms of radiation carcinogenesis may not be simple manifestation of mutation but controlled by much more complex signaling and repair processes.,,
Both the ICRP and BEIR insist to follow LNT principle and practice for cancer risk for radiation exposure for low dose and low dose rates. Recent reports have questioned the LNT hypothesis and have pointed out that experimental results of William Russel conducted on 2 million mice yielded dose rate effect, which means reduced cancer for low dose rate exposures for the same total dose. This partly negated the validity of LNT model, but his results were overshadowed under the powerful scientific influence of Muller who was the chief proponent of LNT model of carcinogenic risk. Interestingly, after the death of Muller in 1967, Russel restated the conclusion of his results and questioned the validity of LNT model at low doses and low dose rate exposures, but the impact of his research remained in the background and did not get significance it deserved.
In a recently published account of LNT model, Calabrese has given a lucid account of events and scientific results and interpretations which aligned with the prevailing opinion of powerful scientists like Muller and his school. In addition, a number of recent publications have raised questions regarding the validity of LNT model predictions of cancer risk from low dose radiation exposures. Based on the recent radiobiological data and nonverified assumption of LNT, its claims are argued to be false and harmful.,, It is striking that 1600 people died in following with the standards of regulatory bodies for radiation protection.
Scott et al. have revisited the arguments in favor of LNT and have raised convincing points against it citing the data in literature on low dose radiation-induced stimulation of built-in cytoprotective strategies of damage repair, upregulation of antioxidant enzymes, activation of immune system, etc., in favor of a threshold of radiation risk. The LNT hypothesis derives its route from incomplete, early 20th century, genetic experimental observations yielding inaccurate conclusions, undetected several new damage and repair paradigms. The Report on concerted studies on nuclear workers and computed tomography data of the UK has demonstrated excess cancer risk among the nuclear occupational workers and diagnostic computed tomography image procedures, but these results have been influenced by other confounding factors than radiation and imprecise dose measurements., Clearly, given the new radiobiological research data and taking into account the presence of repair and defense machineries inside living cells, the LNT-predicted carcinogenic risk at low doses and low dose rate exposures seem to be an overestimate.
It may be prudent to heed to well-established existing phenomenon of adaption after low dose exposures and activation of immune system by low doses of radiation along with the upregulation of antioxidant defense in the evaluation of harm to low dose radiation exposures. It appears reasonable to consider the existence of a threshold dose, below which organisms utilize low dose exposures for beneficial cellular and organ functions rather than predicted but unfounded harmful effects of cancer incidence.
|1||Dobrzynski L, Fornalski KW, Feinendegen LE. Cancer mortality among people living in areas with various levels of natural background radiation. Dose Response 2015;13:1559325815592391.|
|2||Gori T, Münzel T. Biological effects of low-dose radiation: Of harm and hormesis. Eur Heart J 2012;33:292-5.|
|3||Authors on behalf of ICRP, Stewart FA, Akleyev AV, Hauer-Jensen M, Hendry JH, Kleiman NJ, et al. ICRP publication 118: ICRP statement on tissue reactions and early and late effects of radiation in normal tissues and organs – Threshold doses for tissue reactions in a radiation protection context. Ann ICRP 2012;41:1-322.|
|4||Sanders CL. Radiation Hormesis and the Linear-No-Threshold Assumption. Heidelberg-New York: Springer; 2010.|
|5||Pierce DA, Preston DL. Radiation-related cancer risks at low doses among atomic bomb survivors. Radiat Res 2000;154:178-86.|
|6||Preston DL, Cullings H, Suyama A, Funamoto S, Nishi N, Soda M, et al. Solid cancer incidence in atomic bomb survivors exposed in utero or as young children. J Natl Cancer Inst 2008;100:428-36.|
|7||Socol Y, Dobrzynski L. Atomic bomb survivors life-span study: Insufficient statistical power to select radiation carcinogenesis model. Dose Response 2015;13. pii: Dose-response. 14-034. Socol.|
|8||Liu SZ. Cancer control related to stimulation of immunity by low-dose radiation. Dose Response 2006;5:39-47.|
|9||Feinendegen LE, Pollycove M, Neumann RD. Low-dose cancer risk modeling must recognize up-regulation of protection. Dose Response 2009;8:227-52.|
|10||Löbrich M, Rief N, Kühne M, Heckmann M, Fleckenstein J, Rübe C, et al. In vivo formation and repair of DNA double-strand breaks after computed tomography examinations. Proc Natl Acad Sci U S A 2005;102:8984-9.|
|11||Calabrese EJ. The threshold vs. LNT showdown: Dose rate findings exposed flaws in the LNT model part 2. How a mistake led BEIR I to adopt LNT. Environ Res 2016. pii: S0013-935130934-3.|
|12||Siegel JA, Pennington CW, Sacks B, Welsh JS. The birth of the illegitimate linear no-threshold model: An invalid paradigm for estimating risk following low-dose radiation exposure. Am J Clin Oncol 2015. [Epub ahead of Print].|
|13||Siegel JA, Stabin MG. Radar commentary: Use of linear no-threshold hypothesis in radiation protection regulation in the United States. Health Phys 2012;102:90-9.|
|14||Siegel JA, Welsh JS. Does imaging technology cause cancer? Debunking the linear no-threshold model of radiation carcinogenesis. Technol Cancer Res Treat 2016;15:249-56.|
|15||Siegel JA, Pennington CW, Sacks B. Subjecting radiologic imaging to the linear no-threshold hypothesis: A non sequitur of non-trivial proportion. J Nucl Med 2017;58:1-6.|
|16||Boice JD Jr. Radiation epidemiology and recent paediatric computed tomography studies. Ann ICRP 2015;44 1 Suppl: 236-48.|
|17||Richardson DB, Cardis E, Daniels RD, Gillies M, O'Hagan JA, Hamra GB, et al. Risk of cancer from occupational exposure to ionising radiation: Retrospective cohort study of workers in France, the United Kingdom, and the United States (INWORKS). BMJ 2015;351:h5359.|
|18||Scott BR, Sanders CL, Mitchel RE, Boreham DR. CT scans may reduce rather than increase the risk of cancer. J Am Phys Surg 2008;13:8-11.|