The overestimation of medical consequences of low-dose exposures: Cui bono?

Sergei V Jargin

doi:10.4103/ed.ed_13_21

COMMENTARY

Year : 2021 | Volume : 6 | Issue : 3 | Page : 101-107

The overestimation of medical consequences of low-dose exposures: Cui bono?

Sergei V Jargin
Department of Pathology, Peoples' Friendship University of Russia, Moscow, Russia

Date of Submission	24-Jun-2021
Date of Decision	20-Aug-2021
Date of Acceptance	24-Aug-2021
Date of Web Publication	22-Oct-2021

Correspondence Address:
Sergei V Jargin
Department of Pathology, Peoples' Friendship University of Russia, Miklukho-Maklaya 6, Moscow 117198
Russia

Source of Support: None, Conflict of Interest: None

Check

DOI: 10.4103/ed.ed_13_21

Abstract

After the Chernobyl disaster appeared papers overestimating medical consequences of low-dose radiation exposures. Examples have been discussed previously; an updated overview of selected studies is provided here. Various kinds of bias can be found in the epidemiological research reporting elevated health risks from low doses of ionizing radiation: Interpretation of spontaneous conditions as radiation-induced, dose comparisons disregarding the natural background, publication bias, etc. Admittedly, all relevant parameters cannot always be taken into account in epidemiological research. Several examples of potentially biased reports on Mayak Production Association workers and Techa river valley residents are analyzed here. Doubtful correlations between exposures to low radiation doses and nonmalignant conditions, discussed in this commentary, call into question the cause-effect character of such correlations for malignancies revealed by the same scientists. Correlations can be caused or influenced by dose-dependent selection and self-selection. Individuals with higher doses were probably more motivated to undergo medical checkups and given more attention. The medical surveillance of exposed populations is important; but more consideration should be given to potential bias. A promising approach to the study of dose-response relationships are lifelong experiments in different animal species that can reveal the net harm or potential benefit (within a certain range according to the concept of hormesis) from low-dose exposures to ionizing radiation.

Keywords: Cancer risk, Chernobyl accident, east urals radioactive trace, ionizing radiation

How to cite this article:
Jargin SV. The overestimation of medical consequences of low-dose exposures: Cui bono?. Environ Dis 2021;6:101-7

How to cite this URL:
Jargin SV. The overestimation of medical consequences of low-dose exposures: Cui bono?. Environ Dis [serial online] 2021 [cited 2023 Mar 30];6:101-7. Available from: http://www.environmentmed.org/text.asp?2021/6/3/101/329038

Introduction

After the Chernobyl disaster appeared numerous papers, where diseases among residents of contaminated territories were regarded to be radiogenic.^[1],[2],[3] Several articles overestimating Chernobyl consequences were commented previously.^[4],[5],[6] If some earlier publications were doubtful, later ones by the same researchers can be also unreliable so long as the attitude and motivations remain the same. Potential motives in the former Soviet Union included financing, foreign help, international scientific cooperation, and careers.^[5],[6],[7] Moreover, the Chernobyl disaster has been “exploited in attempts to strangle development of atomic energy, the cleanest, safest and practically inexhaustible means to meet the world's energy needs.”^[8] Various kinds of bias can be found in the epidemiological research reporting elevated cancer risks from low radiation doses: Interpretation of sporadic diseases as radiogenic, dose comparisons ignoring natural background, conclusions about incidence increase without appropriate control,^[4],[5] “forcing a positive slope to the relative risk dose-response curve,”^[9] inaccurate citation^[6] etc. Other biases and confounders have been discussed.^[10],[11] A recent example: Statistically significant elevation of the skin cancer risk was detected in the cohort of Mayak Production Association (MPA) employees.^[12] The workers and probably also some medical staff knew personal employment histories, from which cumulated doses could be inferred, potentially influencing the diagnostic quality and self-reference. Doses to the skin were not indicated. The subjects were exposed mainly to γ-radiation characterized by a relatively high penetration depth so that the part of energy absorbed in the skin was proportionately low. No wonder that the “premalignant skin lesions and actinic keratoses… were very rare in members of the study cohort.”^[12]

The Hypothesis

According to our hypothesis, the overestimation of the causality between radiation and certain pathological conditions in the MPA workers and Techa river population started approximately in 2005. Earlier studies reported no increase in cancer incidence at doses below 520 mSv or generally in MPA employees. The existence of a threshold was regarded possible.^{[13],[14],[15],[16]} The morbidity with incapacity for work did not depend on the cumulative dose.^[17] The leukemia risk per 1 Gy was found to be 3.5 times lower in the Techa river population than in survivors of the atomic bombings of Hiroshima and Nagasaki (life span study [LSS]), i.e., effectiveness of the acute impact was expectedly higher than that of protracted or fractionated exposures.^[18],[19] Of note, the risk of solid cancers in LSS tended to decrease with age, whereas in the Techa river cohort it increased,^[18],[19] which is typical for spontaneous cancer and suggestive of the screening effect. No significant increase in cancer morbidity and mortality was found in the residents of territories contaminated due to the 1957 Kyshtym accident, i.e., the east urals radioactive trace (EURT);^[13] while later analyses by the same researchers detected a significant increase in solid cancer mortality versus external control.^[20] As mentioned above, the attitude has changed around 2005: The same researchers started to stress a comparable level of leukemia and solid cancer risk per dose unit in the MPA, Techa river as well as in the LSS cohorts.^{[20],[21],[22],[23],[24]} An explanation of the changed attitude could be new data obtained and modern methods applied at a later date. This is a potential field for further analysis including self-questioning by authors.

Cataracts

A similar tendency has been noticed in regard to radiation-related cataracts. Correlations between the cumulative dose and cataract incidence in the MPA cohort^[25],[26] have been doubted,^[27],[28] which pertains by inference also to another paper.^[29] Reportedly, the risk increase in all dose categories starting from 0.25 to 0.50 Sv was significant versus the 0–0.25 Sv category. Average doses were 0.54 ± 0.061 Gy in men and 0.46 ± 0.01 Gy in women.^[29] Dose-effect relationships were claimed for cataracts; but the well-known correlation of the latter with diabetes mellitus was not confirmed.^{[25],[28],[29]} Supposedly after some criticism,^[28] the topic of diabetes was removed from the subsequent article.^[26] There were no significant associations of the radiation dose with cataract removal surgeries,^[30] which is understandable if the cataracts were diagnosed relatively early in exposed individuals due to an increased attention to their own health and/or attention on the part of medics (dose-dependent selection and self-selection). In accordance with the hypothesis presented above, earlier publications by the same research group asserted that radiation-induced cataracts developed in MPA workers only following moderate-to-severe radiation sickness after exposures ≥4 Sv.^[31] A. K. Guskova, reviewing the data from Russia, indicated that chronic exposures ≤2 Gy were not associated with cataracts.^[32],[33] According to the UNSCEAR, “minimum of 3–5 Gy are required to produce significant opacities in animals which are normally not prone to cataract development, as is the case for man… Minimum stationary opacities have been observed after single doses of 1–2 Gy. More dose is required when fractionated. The threshold for cataract for occupational exposure or lengthy fractionation is in the range of 6–14 Gy.”^[34] Later, UNSCEAR reports and reviews discussed lower thresholds and the no-threshold model of the cataract development.^{[35],[36],[37],[38]} Based predominantly on the epidemiological research, the International Commission on Radiological Protection (ICRP) revised preceding recommendations and proposed a threshold of 0.5 Gy for the development of cataracts.^{[32],[38],[39]} However, not all epidemiological studies support the lower threshold.^[32] The dose-dependent diagnostic efficiency and self-reporting, possibly related to a longer work history and hence to cumulative dose, may explain, for example, the above-average risk of cataracts in radiologic technologists.^[40],[41] The discrepancy has been noticed between the findings for cataract history and cataract surgery, where risks for the latter were lower and generally not significant.^[41] As mentioned above, a similar pattern of significant excess relative risk (ERR) for cataract morbidity but nonsignificant ERR for cataract surgery has been reported in MPA workers.^{[30],[41],[42]} This agrees with the concept of dose-dependent diagnostic efficiency and recording of mild cases not requiring surgery. Among cohorts studied for radiation-associated cataracts, a significant ERR for cataract surgery has been reported only in LSS,^{[37],[41],[43],[44]} where a physiological effect of the acute exposure could have been indeed significant. As for experiments, doses were generally higher than averages in Chernobyl, MPA and Techa river populations. Some experiments in rodents investigated low doses and suggested that genetic factors have an influence on the susceptibility to radiation-induced lens opacities.^{[32],[39],[45]} Effects of low doses are not a priori denied here. Undoubtedly, cataracts can be caused by radiation; but doses and dose rates associated with risks, i.e., potential thresholds should be further studied. There is still a small number of studies that provide explicit biological and mechanistic evidence at doses <2 Gy.^[40],[46]

Cardiovascular Diseases

Elevated risks of nonmalignant diseases (cardiovascular, gastrointestinal, and bronchitis) have been reported in Chernobyl, MPA and Techa river cohorts.^{[47],[48],[49],[50],[51],[52],[53],[54],[55],[56],[57],[58],[59],[60]} The average dose from external γ-radiation was around 0.54 Gy in men and 0.44 Gy in women, for example, in the study, where the frequency of arterial disease of lower limbs was found to be associated with the cumulative external dose.^[61] The frequency of aortal atherosclerosis was significantly higher in MPA workers with cumulative doses ≥0.5 Gy than among those with lower doses; the same for ≥0.025 Gy cumulative liver dose of internal α-radiation.^[51] For cerebrovascular diseases (CeVD) these values were correspondingly ≥0.1 and ≥0.01 Gy.^[50] The ERR of CeVD per dose unit in MPA workers was reportedly even higher than in LSS,^{[50],[58],[62]} where bias could have also been operative. Risks of cardiovascular diseases and in particular, of ischemic heart disease, were found in the Techa River cohort to be higher than those computed on the basis of the linear no-threshold model.^[57] Remarkably, the dose-dependent incidence increase in CeVD and ischemic heart disease among MPA workers was not accompanied by an increase in mortality,^{[28],[54],[62],[63]} which can be explained by a dose-dependent diagnostic efficiency with recording of mild and borderline cases.

According to the same research group, the incidence of CeVD was significantly increased among MPA workers with cumulative external doses ≥0.1 Gy.^[50],[64] In particular, risk estimates by Azizova et al.^[48] were noticed to be significantly higher than those by other researchers.^[65] The UNSCEAR could not make any judgment about immediate causal relationships between exposures ≤1–2 Gy and the excess incidence of cardiovascular or generally of nonmalignant diseases.^[66] According to the ICRP, “there are excess risks of heart disease for patients given radiotherapy with estimated average heart doses of 1–2 Gy (single dose equivalent, after correction for dose fractionation effects).”^[32] The value 1–2 Gy [Table 1] may have resulted from added precaution and/or undervaluation due to bias in epidemiological studies. It is known that patients may develop cardiovascular diseases after radiotherapy with doses to the heart around 40 Gy. Lower doses were discussed,^{[32],[67],[68],[69]} being, however, far above the averages for MPA, Techa River and Chernobyl cohorts. The doses associated with heart injury in experimental animals have also been higher than in the above-named cohorts.^{[32],[70],[71]} In some experiments and epidemiological observations, low doses were protective against atherosclerosis.^[32] In accordance with the hypothesis discussed above, an earlier study found no association between the cumulative dose and frequency of ischemic heart disease in MPA workers.^[72] In the past, long-term observations found no differences of cardiovascular diseases in the latter cohort compared to the general population.^[31]

Table 1: Radiation-related risks of cardiovascular conditions: Examples of potential overestimation versus consensus judgments (commented in the text)

Click here to view

In conclusion of this section, the evidence for a causal relationship of long-term cardiovascular risks with low-dose (<0.5 Gy) exposures is inconsistent and considered to be weak, while biological mechanisms are unclear.^[73] The few low-dose experimental studies existing at the moment emphasize the significance of dose rate in the atherosclerotic plaque formation,^[74] thus indirectly witnessing against the role of radiation as a cause of cardiovascular diseases in human populations chronically exposed to low doses.

Discussion

Doubtful correlations between low-dose exposures and nonmalignant conditions call into question the cause-effect character of such correlations for malignancies revealed by the same scientists.^{[22],[75],[76],[77],[78],[79],[80]} Self-questioning and doubts can stimulate scientific thought; therefore, the authors should reassess interpretations of their results. Questionable data (including those discussed here) are sometimes included into reviews and meta-analysis thus potentially influencing scientific opinions and official judgments. Stressing this problem has been one of the aims of this commentary. The author agrees with Prof. Mark P. Little^[81] that studies of questionable reliability “should therefore probably not be used for epidemiologic analysis, in particular for the Russian worker studies considered here.^{[53],[55],[56],[59]}” This might pertain also to some other studies. Reported dose-effect correlations may be caused or influenced by dose-dependent selection and self-selection noticed in various exposed cohorts.^[82],[83] It can be reasonably assumed that individuals with higher doses would be averagely more motivated to undergo medical checkups and given more attention. Therefore, diagnostics must have been more efficient in people with higher doses. Epidemiological studies can account for some bias, which has not always been the case with Chernobyl-and EURT-related research.^[4],[5],[84] A more efficient blinding could have been helpful. As mentioned above in regard to skin lesions, the workers and probably some medics knew personal employment histories, from which cumulated doses could be inferred, potentially influencing the diagnostic thoroughness and self-reporting.^[12] Uncertainties in some epidemiological research should not cast doubt on this type of studies in general. Researchers are usually aware of possible bias, which may stimulate not only criticism but also constructive scientific thought.

Conclusion

The medical surveillance of cohorts exposed to low-dose ionizing radiation is necessary. Evidently, more consideration should be given to potential bias. The screening effect and increased attention of exposed people to their own health will probably result in future reports of enhanced cancer and other health risks in the areas with elevated anthropogenic or natural radiation background. Furthermore, hidden conflicts of interest and ideological bias should be taken into account, evaluating inclusion criteria of papers in reviews and meta-analysis that cover both sides of the low-dose effect controversy. A promising approach to the study of dose-response relationships is lifelong experiments in different animal species. The average life duration of animals would reflect the net harm or potential benefit (within a certain range according to the concept of hormesis) from low-dose exposures to ionizing radiation.^[85],[86] For such ancient biological phenomena as hormesis, DNA repair and carcinogenesis, data may be conditionally generalizable across species.^[87],[88] Further research using different animal species would add knowledge about their radio sensitivity thus making extrapolations to humans more accurate.^[89] Furthermore, studies combining epidemiological data with the evaluation of molecular markers may help to understand mechanisms and consequences of radiation exposures and the role of inherited sensitivity.^[90] In regard to potential ideological bias, the main strategy should be objective discussion as well as measures in support of scientific integrity to reassure the society that science is impartial and helpful to improve the decision-making.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

References

1.	Cherniaev AL, Antonov NS, Kalmanova EN, et al. Lungs exposed to nuclear catastrophe: One-year therapeutic programme in Chernobyl liquidators group. Schweiz Med Wochenschr 1997;127:165-9.
2.	Lysenko AI, Kirpatovskiĭ ID, Pisarenko SS. Morphological changes in male sexual glands in Kaluga regions contaminated with radionuclides. Arkh Patol 2000;62:27-31.
3.	Yablokov AV, Nesterenko VB, Nesterenko AV. Consequences of the Chernobyl catastrophe for public health and the environment 23 years later. Ann N Y Acad Sci 2009;1181:318-26.
4.	Jargin SV. Overestimation of Chernobyl consequences: Poorly substantiated information published. Radiat Environ Biophys 2010;49:743-5.
5.	Jargin SV. Thyroid cancer after Chernobyl: Obfuscated truth. Dose Response 2011;9:471-6.
6.	Jargin SV. Unfounded statements tending to overestimate Chernobyl consequences. J Radiol Prot 2013;33:881-4.
7.	Koterov AN, Wainson AA. Radiation hormesis and epidemiology of carcinogenesis: 'Never the twain shall meet'. Мed Radiol Radiat Saf 2021;66:36-52.
8.	Jaworowski Z. Observations on the Chernobyl disaster and LNT. Dose Response 2010;8:148-71.
9.	Scott BR. It's time for a new low-dose-radiation risk assessment paradigm-one that acknowledges hormesis. Dose Response 2008;6:333-51.
10.	Sacks B, Meyerson G, Siegel JA. Epidemiology without biology: False paradigms, unfounded assumptions, and specious statistics in radiation science (with Commentaries by Inge Schmitz-Feuerhake and Christopher Busby and a Reply by the Authors). Biol Theory 2016;11:69-101.
11.	Watanabe T, Miyao M, Honda R, Yamada Y. Hiroshima survivors exposed to very low doses of A-bomb primary radiation showed a high risk for cancers. Environ Health Prev Med 2008;13:264-70.
12.	Azizova TV, Bannikova MV, Grigoryeva ES, Rybkina VL. Risk of malignant skin neoplasms in a cohort of workers occupationally exposed to ionizing radiation at low dose rates. PLoS One 2018;13:e0205060.
13.	Buldakov LA, Demin SN, Kosenko MM, Kostiuchenko VA, Koshurnikova NA, Krestinina LIu, et al. The medical sequelae of the radiation accident in the Southern Urals in 1957. Med Radiol (Mosk) 1990;35:11-5.
14.	Kostyuchenko VA, Krestinina LYu. Long-term irradiation effects in the population evacuated from the east-Urals radioactive trace area. Sci Total Environ 1994;142:119-25.
15.	Okladnikova ND, Pesternikova VS, Azizova TV, Sumina MV, Kabasheva NIa, Belyaeva ZD, et al. Health status among the staff at the nuclear waste processing plant. Med Tr Prom Ekol 2000;(6):10-4.
16.	Tokarskaya ZB, Scott BR, Zhuntova GV, Okladnikova ND, Belyaeva ZD, Khokhryakov VF, et al. Interaction of radiation and smoking in lung cancer induction among workers at the Mayak nuclear enterprise. Health Phys 2002;83:833-46.
17.	Kabasheva NIa, Okladnikova ND. The basic dynamic indices and structure of morbidity with temporary loss of work capacity in workers of the reactor industry. Gig Tr Prof Zabol 1992;(8):22-4.
18.	Akleyev AV, Kossenko MM, Krestinina LIu, Shalaginov SA, Degteva MO, Startsev NV. Health status of population exposed to environmental contamination in the Southern Urals. Moscow: Radekon; 2001.
19.	Akleev AV, Preston D, Krestinina LIu. Medical and biological consequences of human's chronic exposure to radiation. Med Tr Prom Ekol 2004;(3):30-6.
20.	Akleyev AV, Krestinina LY, Degteva MO, Tolstykh EI. Consequences of the radiation accident at the Mayak production association in 1957 (the 'Kyshtym Accident'). J Radiol Prot 2017;37:R19-42.
21.	Akleev AV, Krestinina LI. Carcinogenic risk in residents of the Techa riverside villages. Vestn Ross Akad Med Nauk 2010;(6):34-9.
22.	Krestinina LY, Davis FG, Schonfeld S, Preston DL, Degteva M, Epifanova S, et al. Leukaemia incidence in the Techa River Cohort: 1953-2007. Br J Cancer 2013;109:2886-93.
23.	Ostroumova E, Gagnière B, Laurier D, Gudkova N, Krestinina L, Verger P, et al. Risk analysis of leukaemia incidence among people living along the Techa River: A nested case-control study. J Radiol Prot 2006;26:17-32.
24.	Ostroumova E, Preston DL, Ron E, Krestinina L, Davis FG, Kossenko M, et al. Breast cancer incidence following low-dose rate environmental exposure: Techa River Cohort, 1956-2004. Br J Cancer 2008;99:1940-5.
25.	Bragin EV, Azizova TV, Bannikova MV. Risk of senile cataract among nuclear industry workers. Vestn Oftalmol 2017;133:57-63.
26.	Azizova TV, Bragin EV, Hamada N, Bannikova MV. Risk assessment of senile cataract incidence in a cohort of nuclear workers of Mayak Production Association. Med Radiol Radiat Saf 2018;63:15-21.
27.	Tukov AR, Kashirina OG, Azizova TV, Bragin EV, Hamada N, Bannikova MV. Risk assessment of senile cataract incidence in a cohort of nuclear workers of Mayak Production Association. Med Radiol Radiat Saf 2018;63:82.
28.	Soloviev VY, Krasnyuk VI. On possible mistakes in the estimation of radiation risk non-cancer effects in Mayak plant workers. Med Radiol Radiat Saf 2018;63:83-4.
29.	Azizova TV, Bragin EV, Hamada N, Bannikova MV. Risk of cataract incidence in a cohort of Mayak PA workers following chronic occupational radiation exposure. PLoS One 2016;11:e0164357.
30.	Azizova TV, Hamada N, Bragin EV, Bannikova MV, Grigoryeva ES. Risk of cataract removal surgery in Mayak PA workers occupationally exposed to ionizing radiation over prolonged periods. Radiat Environ Biophys 2019;58:139-49.
31.	Okladnikova ND, Sumina MV, Pesternikova VS, Azizova TV, Kabasheva NIa. Long-term consequences of external gamma-radiation according to the results of the observation of the personnel of the first atomic power plant in the country. Klin Med (Mosk) 2007;85:21-6.
32.	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.
33.	Guskova AK. Fifty years of the nuclear industry in Russia – Through the eyes of a physician. At Energy 1999;87:903-8.
34.	UNSCEAR 1982 Report. Annex J: Non-Stochastic Effects of Irradiation. New York: United Nations; 1982.
35.	Ainsbury EA, Bouffler SD, Dörr W, Graw J, Muirhead CR, Edwards AA, et al. Radiation cataractogenesis: A review of recent studies. Radiat Res 2009;172:1-9.
36.	Hammer GP, Scheidemann-Wesp U, Samkange-Zeeb F, Wicke H, Neriishi K, Blettner M. Occupational exposure to low doses of ionizing radiation and cataract development: A systematic literature review and perspectives on future studies. Radiat Environ Biophys 2013;52:303-19.
37.	Little MP. A review of non-cancer effects, especially circulatory and ocular diseases. Radiat Environ Biophys 2013;52:435-49.
38.	Uwineza A, Kalligeraki AA, Hamada N, Jarrin M, Quinlan RA. Cataractogenic load – A concept to study the contribution of ionizing radiation to accelerated aging in the eye lens. Mutat Res Rev Mutat Res 2019;779:68-81.
39.	McCarron RA, Barnard SG, Babini G, Dalke C, Graw J, Leonardi S, et al. Radiation-induced lens opacity and cataractogenesis: A lifetime study using mice of varying genetic backgrounds. Radiat Res 2021; [doi: 10.1667/RADE-20-00266.1] Epub ahead of print.
40.	Ainsbury EA, Dalke C, Hamada N, Benadjaoud MA, Chumak V, Ginjaume M, et al. Radiation-induced lens opacities: Epidemiological, clinical and experimental evidence, methodological issues, research gaps and strategy. Environ Int 2021;146:106213.
41.	Little MP, Cahoon EK, Kitahara CM, Simon SL, Hamada N, Linet MS. Occupational radiation exposure and excess additive risk of cataract incidence in a cohort of US radiologic technologists. Occup Environ Med 2020;77:1-8.
42.	Azizova TV, Hamada N, Grigoryeva ES, Bragin EV. Risk of various types of cataracts in a cohort of Mayak workers following chronic occupational exposure to ionizing radiation. Eur J Epidemiol 2018;33:1193-204.
43.	Neriishi K, Nakashima E, Akahoshi M, Hida A, Grant EJ, Masunari N, et al. Radiation dose and cataract surgery incidence in atomic bomb survivors, 1986-2005. Radiology 2012;265:167-74.
44.	Shore RE. Radiation and cataract risk: Impact of recent epidemiologic studies on ICRP judgments. Mutat Res Rev Mutat Res 2016;770:231-7.
45.	Worgul BV, Smilenov L, Brenner DJ, Vazquez M, Hall EJ. Mice heterozygous for the ATM gene are more sensitive to both X-ray and heavy ion exposure than are wildtypes. Adv Space Res 2005;35:254-9.
46.	Ainsbury EA, Barnard S, Bright S, Dalke C, Jarrin M, Kunze S, et al. Ionizing radiation induced cataracts: Recent biological and mechanistic developments and perspectives for future research. Mutat Res Rev Mutat Res 2016;770:238-61.
47.	Azizova TV, Muirhead CR, Druzhinina MB, Grigoryeva ES, Vlasenko EV, Sumina MV, et al. Cardiovascular diseases in the cohort of workers first employed at Mayak PA in 1948-1958. Radiat Res 2010;174:155-68.
48.	Azizova TV, Muirhead CR, Moseeva MB, Grigoryeva ES, Sumina MV, O'Hagan J, et al. Cerebrovascular diseases in nuclear workers first employed at the Mayak PA in 1948-1972. Radiat Environ Biophys 2011;50:539-52.
49.	Azizova TV, Zhuntova GV, Haylock RG, Moseeva MB, Grigoryeva ES, Hunter N, et al. Chronic bronchitis in the cohort of Mayak workers first employed 1948-1958. Radiat Res 2013;180:610-21.
50.	Azizova TV, Haylock RG, Moseeva MB, Bannikova MV, Grigoryeva ES. Cerebrovascular diseases incidence and mortality in an extended Mayak Worker Cohort 1948-1982. Radiat Res 2014;182:529-44.
51.	Azizova TV, Kuznetsova KV, Bannikova MV, Sumina MV, Bagaeva IaP, Azizova EV, et al. Prevalence of aortal atherosclerosis in workers underwent occupational irradiation. Med Tr Prom Ekol 2014;(11):1-6.
52.	Azizova TV, Bannikova MV, Moseeva MV, Grigor'eva ES, Krupenina LN. Cerebrovascular disease incidence in workers occupationally exposed to radiation over prolonged time periods. Zh Nevrol Psikhiatr Im S S Korsakova 2014;114:128-32.
53.	Azizova TV, Grigoryeva ES, Haylock RG, Pikulina MV, Moseeva MB. Ischaemic heart disease incidence and mortality in an extended cohort of Mayak workers first employed in 1948-1982. Br J Radiol 2015;88:20150169.
54.	Azizova TV, Haylock R, Moseeva MB, Pikulina MV, Grigorieva ES. Cerebrovascular diseases incidence and mortality in an extended Mayak Worker Cohort: 1948-1982. Med Radiol Radiat Saf 2015;(4)43-61.
55.	Ivanov VK, Maksioutov MA, Chekin SY, Petrov AV, Biryukov AP, Kruglova ZG, et al. The risk of radiation-induced cerebrovascular disease in Chernobyl emergency workers. Health Phys 2006;90:199-207.
56.	Kashcheev VV, Chekin SY, Maksioutov MA, Tumanov KA, Menyaylo AN, Kochergina EV, et al. Radiation-epidemiological study of cerebrovascular diseases in the cohort of Russian recovery operation workers of the Chernobyl accident. Health Phys 2016;111:192-7.
57.	Krestinina LY, Epifanova S, Silkin S, Mikryukova L, Degteva M, Shagina N, et al. Chronic low-dose exposure in the Techa River Cohort: Risk of mortality from circulatory diseases. Radiat Environ Biophys 2013;52:47-57.
58.	Moseeva MB, Azizova TV, Muirhed CR, Grigor'eva ES, Vlasenko EV, Sumina MV, et al. Risk of cerebrovascular disease incidence in the cohort of Mayak production association workers first employed during 1948-1958. Radiats Biol Radioecol 2012;52:149-57.
59.	Moseeva MB, Azizova TV, Grigoryeva ES, Haylock R. Risks of circulatory diseases among Mayak PA workers with radiation doses estimated using the improved Mayak Worker Dosimetry System 2008. Radiat Environ Biophys 2014;53:469-77.
60.	Yablokov AV. 5. Nonmalignant diseases after the Chernobyl catastrophe. Ann N Y Acad Sci 2009;1181:58-160.
61.	Azizova TV, Bannikova MV, Grigorieva ES, Bagaeva YP, Azizova EV. Risk of lower extremity arterial disease in a cohort of workers occupationally exposed to ionizing radiation over a prolonged period. Radiat Environ Biophys 2016;55:147-59.
62.	Azizova TV, Muirhead CR, Druzhinina MB, Grigoryeva ES, Vlasenko EV, Sumina MV, et al. Cerebrovascular diseases in the cohort of workers first employed at Mayak PA in 1948-1958. Radiat Res 2010;174:851-64.
63.	Azizova TV, Moseeva MB, Grigor'eva ES, Muirhed CR, Hunter N, Haylock RG, et al. Mortality risk of cardiovascular diseases for occupationally exposed workers. Radiats Biol Radioecol 2012;52:158-66.
64.	Simonetto C, Schöllnberger H, Azizova TV, Grigoryeva ES, Pikulina MV, Eidemüller M. Cerebrovascular diseases in workers at Mayak PA: The difference in radiation risk between incidence and mortality. PLoS One 2015;10:e0125904.
65.	Rühm W, Breckow J, Dietze G, Friedl A, Greinert R, Jacob P, et al. Dose limits for occupational exposure to ionising radiation and genotoxic carcinogens: A German perspective. Radiat Environ Biophys 2020;59:9-27.
66.	UNSCEAR 2006 Report. Annex B: Epidemiological Evaluation of Cardiovascular Disease and Other Non-Cancer Diseases Following Radiation Exposure. New York: United Nations; 2006.
67.	National Research Council. Health Risks from Exposure to Low Levels of Ionizing Radiation: BEIR VII Phase 2. Washington, DC: The National Academies Press; 2006.
68.	Baselet B, Rombouts C, Benotmane AM, Baatout S, Aerts A. Cardiovascular diseases related to ionizing radiation: The risk of low-dose exposure (Review). Int J Mol Med 2016;38:1623-41.
69.	Darby SC, Cutter DJ, Boerma M, Constine LS, Fajardo LF, Kodama K, et al. Radiation-related heart disease: Current knowledge and future prospects. Int J Radiat Oncol Biol Phys 2010;76:656-65.
70.	Schultz-Hector S. Radiation-induced heart disease: Review of experimental data on dose response and pathogenesis. Int J Radiat Biol 1992;61:149-60.
71.	UNSCEAR 1962 Report. Annex D: Somatic Effects of Radiation. New York: United Nations; 1962.
72.	Dudchenko NN, Okladnikova ND. Ischemic heart disease in workers of radiochemical industry chronically exposed to radiation dosage less than MPEL. Med Tr Prom Ekol 1995;(6):7-10.
73.	Kreuzer M, Auvinen A, Cardis E, Hall J, Jourdain JR, Laurier D, et al. Low-dose ionising radiation and cardiovascular diseases – Strategies for molecular epidemiological studies in Europe. Mutat Res Rev Mutat Res 2015;764:90-100.
74.	Tapio S, Little MP, Kaiser JC, Impens N, Hamada N, Georgakilas AG, et al. Ionizing radiation-induced circulatory and metabolic diseases. Environ Int 2021;146:106235.
75.	Azizova TV, Korobkin AV, Osovets SV, Bannikova MV. Latency Period of Acute Leukaemia in the Cohort of Mayak Workers. In: Chronic Radiation Exposure: Low-Dose Effects. In: Abstracts of the 4^th International Conference. Chelyabinsk, Russia; 9-11 November, 2010. p. 14-5.
76.	Ivanov VK, Gorski AI, Tsyb AF, Ivanov SI, Naumenko RN, Ivanova LV. Solid cancer incidence among the Chernobyl emergency workers residing in Russia: Estimation of radiation risks. Radiat Environ Biophys 2004;43:35-42.
77.	Krestinina LY, Davis F, Ostroumova E, Epifanova S, Degteva M, Preston D, et al. Solid cancer incidence and low-dose-rate radiation exposures in the Techa River cohort: 1956 2002. Int J Epidemiol 2007;36:1038-46.
78.	Sokolnikov ME, Gilbert ES, Preston DL, Ron E, Shilnikova NS, Khokhryakov VV, et al. Lung, liver and bone cancer mortality in Mayak workers. Int J Cancer 2008;123:905-11.
79.	Sokolnikov M, Preston D, Gilbert E, Schonfeld S, Koshurnikova N. Radiation effects on mortality from solid cancers other than lung, liver, and bone cancer in the Mayak worker cohort: 1948-2008. PLoS One 2015;10:e0117784.
80.	Yablokov AV. 6. Oncological diseases after the Chernobyl catastrophe. Ann N Y Acad Sci 2009;1181:161-91.
81.	Little MP. Radiation and circulatory disease. Mutat Res 2016;770 (Pt B):299-318.
82.	McGeoghegan D, Binks K, Gillies M, Jones S, Whaley S. The non-cancer mortality experience of male workers at British Nuclear Fuels plc, 1946-2005. Int J Epidemiol 2008;37:506-18.
83.	Zablotska LB, Bazyka D, Lubin JH, Gudzenko N, Little MP, Hatch M, et al. Radiation and the risk of chronic lymphocytic and other leukemias among Chornobyl cleanup workers. Environ Health Perspect 2013;121:59-65.
84.	Jargin SV. The Overestimation of Medical Consequences of Low-Dose Exposure to Ionizing Radiation. Newcastle upon Tyne: Cambridge Scholars Publishing; 2019.
85.	Braga-Tanaka I 3^rd, Tanaka S, Kohda A, Takai D, Nakamura S, Ono T, et al. Experimental studies on the biological effects of chronic low dose-rate radiation exposure in mice: Overview of the studies at the Institute for Environmental Sciences. Int J Radiat Biol 2018;94:423-33.
86.	Calabrese EJ, Baldwin LA. Radiation hormesis: Its historical foundations as a biological hypothesis. Hum Exp Toxicol 2000;19:41-75.
87.	Calabrese EJ. Model uncertainty via the integration of hormesis and LNT as the default in cancer risk assessment. Dose Response 2015;13:1559325815621764.
88.	Baldwin J, Grantham V. Radiation hormesis: Historical and current perspectives. J Nucl Med Technol 2015;43:242-6.
89.	Higley KA, Kocher DC, Real AG, Chambers DB. Relative biological effectiveness and radiation weighting factors in the context of animals and plants. Ann ICRP 2012;41:233-45.
90.	Bilous N, Abramenko I, Chumak A, Dyagil I, Martina Z. MYC copy number and mRNA expression in chronic lymphocytic leukemia patients exposed to ionizing radiation due to the Chornobyl NPP accident. Exp Oncol 2020;42:60-5.