Monte Carlo Simulation-Based Calculations of Complex DNA Damage for Incidents of Environmental Ionizing Radiation Exposure

Round 1

Reviewer 1 Report

By use of Monte Carlo simulations, Kalospyros et al. calculated the absorbed dose and the number of induced DNA damage in the cells of an individual exposed to ionizing radiation from Cs-137 source deposited on the ground surface after a nuclear accident. The authors also estimated the cancer risk of hypothetical individuals.

The purpose of the study is neither clearly nor concisely described, and the manuscript does not contain enough data to provide a significant insight into radiation science. I suggest that the manuscript should be declined. The criticisms are as follows;

1. Figure 2: Accuracy of calculation was not confirmed by comparing with an actual measurement.
2. Figure 3: Scientifically significant insight could not be provided from the data, because the numbers of DSBs and SSBs seem to be simply proportional to absorbed dose shown in Figure 2.
3. Figure 4 and 5: Scientifically significant insight could not be provided from the data, because the absorbed dose and numbers of DSBs and SSBs seem to be simply proportional to exposure time.
4. Table 1: To determine ELCR, only absorbed dose was utilized, and the number of DNA damages were not used. The rationale behind that the authors calculated DNA damage yield is unclear. In addition, the reason why specific organs were selected for each individual is unclear. Furthermore, the estimated ELCR is considered to contain a large error because people did not keep standing on the ground for the total time of exposure.

Author Response

All authors would like to sincerely thank all three (3) reviewers and the Editor for their constructive comments and time and effort to review our work. We have performed an extensive revision addressed all comments and problems or questions raised.

The purpose of the study is stated now more clearly and it was to provide a simulation of the dose distribution and biological effects in the case of an environmental exposure of a human being to ionizing radiation (low-LET).

We are aware that with the current study there are limitations that we tried to extend and provide more accurate and specific data on different exposure scenarios. We understand that it is difficult to cover all cases but the study is original and we hope that it will be well-appreciated by the radiation community and will provide a useful set of data for researchers worldwide to compare and use our results. Generally, our methodology has proved to be useful for assessing γ rays-induced DNA damage levels of the exposed population in the case of a REI and better understanding of the long-term health effects of exposure of the population to IR.

 

REVIEWER #1:

The authors would like to express their thanks to the Reviewer for the time considering this study and for supplying really constructive comments. His comments helped us to correct our oversights and present a better manuscript for the readers of this Journal. We really thank him.

The purpose of the study is neither clearly nor concisely described, and the manuscript does not contain enough data to provide a significant insight into radiation science.

Response: We apologize that the manuscript in its 1^st version was not sufficiently clear enough. We made a major effort so that the 2nd version of our manuscript has improved towards clarity based also on the rigid comments of the reviewer, originating mainly from the topic that is elaborated. We believe that the work is original towards combining all different aspects from radiation to damage simulations and cancer risk calculation. We believe, that now we present an optimized and useful Monte Carlo (MC)-based methodology that can be utilized to calculate the absorbed dose and the initial levels of complex DNA damage in the case of an environmental ionizing radiation (IR) exposure incident (REI) like a nuclear accident. This idea and study is original.

Please mind that there are some unconnected gaps in our knowledge of the radiation effects in the cellular level till the later stages of the cell’s response and possible early stages of carcinogenesis. On the other hand, in the case of a REI, such as a nuclear accident that we refer to, there is always a difficulty in isolating one of the radiation components from the radionuclides which are released in the environment during such incidents (see added clause in the abstract). For this reason, we have used the Monte Carlo (MC) techniques which are the most suitable tools for simulating the basic ways of interaction between radiation and biological matter. We have used a combination of two different codes; the first one, MCNP is a multipurpose and widely accepted MC code for the accuracy of its results that calculates spectra (photon, electron cascades, nuclear reactions and responses) covering nuclear and medical applications. The second one, MCDS has the ability to simulate in a fast way (seconds-some minutes) the induction and clustering of DNA lesions. Their combined use gave us the opportunity to calculate the absorbed dose due to the irradiation of ¹³⁷Cs from the ground and the number of SSBs and DSBs induced by it. Due to the fact that the prompt connection between these induced DNA lesions and the cancer process is still under research, and because the scientific community has not the ability to connect the quantification of these lesions to the possibility of cancer onset, we calculated the number of the induced DNA damage and handed them over for any future relevant use by the scientific community.

At the same time, by the use of the absorbed dose as a physical quantity extracted from the MCNP code, we applied it for the estimation of a useful cancer risk type for hypothetical individuals exposed to different time periods in an area contaminated with ¹³⁷Cs radionuclide. Thus, making certain modifications in our first manuscript, thanks to this Reviewer, we report our results about DNA damage for any future use of them by the scientific community.

 The criticisms are as follows;

 Figure 2: Accuracy of calculation was not confirmed by comparing with an actual measurement.

 Response: The Reviewer’s comment is valid and very correct according also with our opinion. Fig.2 shows only the results extracted from the MCNP6.1 code of the absorbed dose vs the height from the ground. Our results COULD be always compared with others’ of an actual experimental measurement which we did not find; Therefore, in this case, we did not use any comparison of this kind based also on the fact that the used MC code is widely acknowledged as very accurate and trustworthy for calculations of this kind (especially, version 6.1 has the ability to describe the electron transport down to 10 eV with great accuracy [1]). We hope in the future us or others would be able to perform such tasks.

Figure 3: Scientifically significant insight could not be provided from the data, because the numbers of DSBs and SSBs seem to be simply proportional to absorbed dose shown in Figure 2.

Figure 4 and 5: Scientifically significant insight could not be provided from the data, because the absorbed dose and numbers of DSBs and SSBs seem to be simply proportional to exposure time

 

Response: The authors understand the Reviewer’s concern for scientifically insightful results of a new paper. Our results were extracted through MC codes based on either databases embedded in the program with the inclusion of internationally recognized libraries of cross sections (MCNP) or parameters formed on track structure simulations from recognized research papers (see: Nikjoo et al. [2,3], Friedland et al. [4]) of the bibliography (MCDS) [5,6]. In the very low dose range, the estimates are based on a linear extrapolation of high dose data obtained from the study of atomic bomb survivors; the linear-no-threshold model (LNT) is based on the assumption that the DNA damage is proportional to the dose and that the response of the irradiated cell is equally efficient from high to low dose. In our results, we note the trend of linearity between the numbers of DNA lesions and the absorbed dose (and exposure time). This linear trend confirms in part the LNT model, since we know that there are also phenomena such as the low-dose hypersensitivity, the adaptive and hormetic response, the bystander effect and the threshold hypothesis [7-9] which unsettle the validity of the linear extrapolation. We do not extract experimental results obtained in vitro, and so we did not expect these results of us to have a decline from the rule. But, we mention this fact in our new manuscript, justifying and combining it with references from the contemporary international bibliography (see L.460-494).

 

Table 1: To determine ELCR, only absorbed dose was utilized, and the number of DNA damages were not used. The rationale behind that the authors calculated DNA damage yield is unclear. In addition, the reason why specific organs were selected for each individual is unclear. Furthermore, the estimated ELCR is considered to contain a large error because people did not keep standing on the ground for the total time of exposure.

 

Response:  The Reviewer is right. Through the combination of two different MC codes we calculated the absorbed dose and estimated the DNA damage for the radiation of the ‘standing man’ by the ¹³⁷Cs under his feet for different values of surface activity and exposure times. We made no use of the number of DNA lesions when determining ELCR. But, in our new manuscript, we emphasized that there is no clear physico-mathematical description of the microscopic connection between radiation of a cell/tissue and carcinogenesis, that could be used in such a code (see L.648-651). For this reason, we used the official and widely known NCI tool, an online calculator for the estimate of the ELCR, in which we may enter the absorbed dose and other time data for the hypothetical individuals exposed to the radiation released after the nuclear accident of Chernobyl. Unfortunately and as we speak, DNA damage yields resulted from any MC code or even experimental cannot be connected promptly to any cancer risk estimate derived from any competent calculator or algorithm. Our quantification of the DNA lesions in this simulation was commented in association with the absorbed dose, which – as justified in relation to bibliography – approximates the lowest limit of radiation dose for the formation of DSBs (see L.589-605). And since at such low doses of radiation, there seems to be no repair process by the cell itself (see L.517-533), we may bypass a basic disadvantage of the MCDS code which does not include any repair process. On the other hand, the extracted number of SSBs and DSBs can be used for any relevant future research from the scientific community.

      From the group of the 8 hypothetical individuals that we have considered, our selection of specific organs has been based on the sensitivity of the human tissues to radiation (having excluded the thyroid gland which is closely connected to the intake of ¹³¹I), the availability of these organs in the NCI tool and the volume that they occupy in the human body; in the latter criterion, our purpose was to examine only compact and not extended organs so that we can use a certain dose value in relation to the height from the ground where this organ lies in the body (see L.670-681).

       We also considered certain exposure time for every individual that we examined, having explained (see L.634-638 & L.665-667) that the real exposure time is longer than the considered one, due to the fact that no one could keep standing for the total time of exposure. The estimated ELCR may contain an error, and so we have commented on it (see L.665-667) considering in reality a time extension of the referred exposure time. We have also commented on the limitations of our study (see L.799-820).

References

1. Goorley, J.T. Initial mcnp6 release overview - mcnp6 version 1.0.
2. Nikjoo, H.; O'Neill, P.; Terrissol, M.; Goodhead, D.T. Modelling of radiation-induced DNA damage: The early physical and chemical event. International journal of radiation biology 1994, 66, 453-457.
3. Nikjoo, H.; O'Neill, P.; Goodhead, D.T.; Terrissol, M. Computational modelling of low-energy electron-induced DNA damage by early physical and chemical events. International journal of radiation biology 1997, 71, 467-483.
4. Friedland, W.; Dingfelder, M.; Jacob, P.; Paretzke, H.G. Calculated DNA double-strand break and fragmentation yields after irradiation with he ions. Radiation Physics and Chemistry 2005, 72, 279-286.
5. Semenenko, V.A.; Stewart, R.D. Fast monte carlo simulation of DNA damage formed by electrons and light ions. Phys Med Biol 2006, 51, 1693-1706.
6. Semenenko, V.A.; Stewart, R.D. A fast monte Carlo algorithm to simulate the spectrum of DNA damages formed by Ionizing Radiation, Radiation Research 2004, 161, 451-457.
7. Brenner DJ, Doll R, Goodhead DT, Hall EJ, Land CE, Little JB, Lubin JH, Preston DL, Preston RJ, Puskin JS, et al: Cancer risks attributable to low doses of ionizing radiation: Assessing what we really know. Proc Natl Acad Sci USA 2003, 100: 13761-13766,
8. Averbeck D. Does scientific evidence support a change from the LNT model for low-dose radiation risk extrapolation? Health Phys 2009, 97: 493‑504.
9. Averbeck D: Non-targeted effects as a paradigm breaking evidence. Mutat Res 2010, 687: 7-12.
10. Berlizov, A N, MCNP-CP: A Correlated Particle Radiation Source Extension of a General Purpose Monte Carlo N-Particle Transport Code, 2006, ACS Symposium Series 945:183-194.

Reviewer 2 Report

• The authors could add some comments relating to more recent studies, in areas not adjacent to the area affected by Chernobyl accident, after about 30 years. Indeed, some plants and the lichens, were widely used in the biomonitoring researches for spatial and temporal deposition patterns of radionuclides, especially radiocaesium  (consistent with the element's half-life). [Savino et al. 2017, Chiaravalle et al. 2018]. A similar issue concerned the 2011 Fukushima incident. [DohiI et al. 2021].

 

• Figures 2 and 3b are practically the same, could the authors check that there are no mistakes? Could they possibly compare and interpret these two trends?

 

 

• Line 497, there is a mistype ]

 

• The authors state that one of the outputs obtained with the MCNP tool is the e-secondary spectrum and that this becomes the input for the MCDS tool. It would be interesting to be able to observe the trend of this spectrum in a picture.

 

• The authors could better explain the transition from determining DSBs and SSBs to calculating of the ELCR. I understand that MCDS simulates the so called "initial" levels of DNA damage induced and not the processing of repair, this of course provides a limit for the study of late effects, therefore not observable on a long-term scale. Is there a link between the calculations performed with the coupling MCNP - MCDS with that relating to ELCR?

 

• With regard to the assessment of ELCR and risk grade, the authors define leukemia as low risk but other studies have instead shown that leukemia is a very common side effect of exposure to these accidents, especially in childhood. The authors could enlarge the discussion by also comparing their results with those obtained in other studies [Ivanov E.P. et al. 1998; [Ivanov V.K. et al. 2012; Noshchenko et al. 2010].

Author Response

All authors would like to sincerely thank all three (3) reviewers and the Editor for their constructive comments and time and effort to review our work. We have performed an extensive revision addressed all comments and problems or questions raised.

The purpose of the study is stated now more clearly and it was to provide a simulation of the dose distribution and biological effects in the case of an environmental exposure of a human being to ionizing radiation (low-LET).

We are aware that with the current study there are limitations that we tried to extend and provide more accurate and specific data on different exposure scenarios. We understand that it is difficult to cover all cases but the study is original and we hope that it will be well-appreciated by the radiation community and will provide a useful set of data for researchers worldwide to compare and use our results. Generally, our methodology has proved to be useful for assessing γ rays-induced DNA damage levels of the exposed population in the case of a REI and better understanding of the long-term health effects of exposure of the population to IR.

REVIEWER #2:

Comments and Suggestions for Authors

The authors would like to thank the Reviewer for his creative comments which helped us to modify our manuscript in an optimal way.

 

The authors could add some comments relating to more recent studies, in areas not adjacent to the area affected by Chernobyl accident, after about 30 years. Indeed, some plants and the lichens, were widely used in the biomonitoring researches for spatial and temporal deposition patterns of radionuclides, especially radiocaesium (consistent with the element's half-life). [Savino et al. 2017, Chiaravalle et al. 2018]. A similar issue concerned the 2011 Fukushima incident. [DohiI et al. 2021].

 

 Response: The Reviewer has stated wisely something that had eluded our attention until now. Really, some plants and especially lichens are widely used in such biomonitoring researches; Since lichens have no roots, they absorb much of their raw materials directly from the air and moisture from the nearest environment. This characteristic makes them very sensitive to air pollutants and radionuclides and since these plants have no way to excrete these chemical species that they absorb, the latter stay inside their cells. Then the incorporated radionuclides may accumulate over time, reaching high contamination levels which are appreciable even many years after any REI, despite the expected decay with time. We have added the suggested references with the relevant comments in our new manuscript (see L.135-144 & L.181-185).

 

Figures 2 and 3b are practically the same, could the authors check that there are no mistakes? Could they possibly compare and interpret these two trends?

 Response: We appreciate the comment of the Reviewer but please let us explain this point better. From a quick look, these two graphs seem to be the same. But in practice, they show a decrease trend of the absorbed dose and the induced SSBs with the increase of height from the ground (source); this happens because an increase in the distance from the source is equivalent to the reduction of the number of photons which penetrate a surface along the direction of the radiation. The dose becomes quite constant after the first centimeters from the ground (the latter distance varies in relation to the surface activity of the ¹³⁷Cs); this distance is also the range of γ-rays in the air. There is a clear linearity between the induced DNA lesions and the absorbed dose as also suggested by a wide range of theoretical and experimental studies. This trend could support in part the linear-no-threshold (LNT) model; this assumes that the DNA damage is proportional to the dose and the cellular response to radiation operates equally efficiently from high to low doses. Of course, there are phenomena, such as the low-dose hypersensitivity, the adaptive and hormetic response, the bystander effect and the threshold hypothesis [7-9] which affect the validity of the linear extrapolation of high dose data obtained from the study of atomic bomb survivors to the low dose region. We have added new comments about this in the corrected manuscript (see L.462-483).

 

Line 497, there is a mistype ]

Response: We have corrected this error rewriting the clause (see L.776-777).

 

The authors state that one of the outputs obtained with the MCNP tool is the e-secondary spectrum and that this becomes the input for the MCDS tool. It would be interesting to be able to observe the trend of this spectrum in a picture.

Response:

 

see fig in the attached file REVIEWER #2....

https://www.dropbox.com/s/0y0oko36ovwmvjh/Response%20to%20Reviewer%202.png?dl=0

  We selected randomly one of the output cards of the MCNP6.1 code (for the height 40 cm from the source) and we depict the secondary electron spectrum (by γ-radiation) in a 3-D graph (through the MatLab packet). Energy is measured in MeV and the distance from the source in cm.

 

The authors could better explain the transition from determining DSBs and SSBs to calculating of the ELCR. I understand that MCDS simulates the so called "initial" levels of DNA damage induced and not the processing of repair, this of course provides a limit for the study of late effects, therefore not observable on a long-term scale. Is there a link between the calculations performed with the coupling MCNP - MCDS with that relating to ELCR?

Response: The MCDS code does not involve the process of DNA repair in its results and thus, in our study we take into account the existed bibliography in order to translate the estimated number of SSBs & DSBs into cancer risk information. Additionally, many studies indicate that in the range of very low doses, as this in our work, the induced DSBs remain unrepaired for many days or even completely unrepaired. On the other hand, un- or mis-repaired DSBs may give rise to chromosomal aberrations and other structures which denote genomic instability; this may lead a cell through different slow stages to oncogenic transformation. Thus, we added new extended comments in our new manuscript (see L.460-605 & L.648-651) ‘filling’ the gap between the estimated numbers of DNA damage and the calculation of the ELCR through the NCI tool. The latter requires only the absorbed dose and no other physical quantities, being, at the same time, a reliable and useful tool for the calculation of the ELCR for different body organs estimated in a certain height from the ground. Cancer is a multistage and multifactorial process and in order to assess any risk estimate with the most accurate approach possible for it, one has to investigate at the same time all the factors associated with this disease. In our new added comments we stress the sensitivity to radiation of certain tissues (e.g. the thyroid gland, the female breast, etc.) (see L.544-550 & L.551-567) and we associate it to the observed carcinogenesis. The calculated DNA damage constitutes a characteristic sample of unrepaired lesions which quantified may be used for any future research by the scientific community.

 

With regard to the assessment of ELCR and risk grade, the authors define leukemia as low risk but other studies have instead shown that leukemia is a very common side effect of exposure to these accidents, especially in childhood. The authors could enlarge the discussion by also comparing their results with those obtained in other studies [Ivanov E.P. et al. 1998; [Ivanov V.K. et al. 2012; Noshchenko et al. 2010].

Response: Yes, this is true: in the results of our study, we have referred to leukemia with a low risk grade estimation (ELCR), although this disease is one of the representatives of the side effects after exposure to radiation in the contemporary bibliography and through the studies of atomic bomb survivors. But this happens due to the selected short time of exposure of the hypothetical individual. Taking into account that the objective of our study is to calculate the absorbed dose and estimate the DNA damage, by isolating only one component (the radiation emitted by the ¹³⁷Cs in the ground) of the total radiation released in the environment after a nuclear accident, for an individual standing on the ground (we have added this basic comment to the abstract, see L.19-22), we examined also leukemia as a characteristic side effect and estimated its ELCR. The extracted risk possibility depends also on the exposure time of the affected-by-radiation individual. Cancer is a multistage and multifactorial process and in order to assess any risk estimate with the most accurate approach possible for cancer, one has to investigate at the same time all the factors associated with this disease (environmental factors, dietary habits, etc). Our estimate was only representative of this specific after-radiation side effect, very common among people exposed to a REI, and its reference in our study had only this goal. We have added comments on the case of leukemia in relation to the suggested (and more) references by the Reviewer (see L.601-605, L.606-609, L.738-766 & L.799-820).

 

References

1. Goorley, J.T. Initial mcnp6 release overview - mcnp6 version 1.0.
2. Nikjoo, H.; O'Neill, P.; Terrissol, M.; Goodhead, D.T. Modelling of radiation-induced DNA damage: The early physical and chemical event. International journal of radiation biology 1994, 66, 453-457.
3. Nikjoo, H.; O'Neill, P.; Goodhead, D.T.; Terrissol, M. Computational modelling of low-energy electron-induced DNA damage by early physical and chemical events. International journal of radiation biology 1997, 71, 467-483.
4. Friedland, W.; Dingfelder, M.; Jacob, P.; Paretzke, H.G. Calculated DNA double-strand break and fragmentation yields after irradiation with he ions. Radiation Physics and Chemistry 2005, 72, 279-286.
5. Semenenko, V.A.; Stewart, R.D. Fast monte carlo simulation of DNA damage formed by electrons and light ions. Phys Med Biol 2006, 51, 1693-1706.
6. Semenenko, V.A.; Stewart, R.D. A fast monte Carlo algorithm to simulate the spectrum of DNA damages formed by Ionizing Radiation, Radiation Research 2004, 161, 451-457.
7. Brenner DJ, Doll R, Goodhead DT, Hall EJ, Land CE, Little JB, Lubin JH, Preston DL, Preston RJ, Puskin JS, et al: Cancer risks attributable to low doses of ionizing radiation: Assessing what we really know. Proc Natl Acad Sci USA 2003, 100: 13761-13766,
8. Averbeck D. Does scientific evidence support a change from the LNT model for low-dose radiation risk extrapolation? Health Phys 2009, 97: 493‑504.
9. Averbeck D: Non-targeted effects as a paradigm breaking evidence. Mutat Res 2010, 687: 7-12.
10. Berlizov, A N, MCNP-CP: A Correlated Particle Radiation Source Extension of a General Purpose Monte Carlo N-Particle Transport Code, 2006, ACS Symposium Series 945:183-194.

Reviewer 3 Report

Please follow the attached file with my comments and suggestions for the authors.

Comments for author File: Comments.docx

Author Response

RESPONSES TO THE REVIEWERS

All authors would like to sincerely thank all three (3) reviewers and the Editor for their constructive comments and time and effort to review our work. We have performed an extensive revision addressed all comments and problems or questions raised.

The purpose of the study is stated now more clearly and it was to provide a simulation of the dose distribution and biological effects in the case of an environmental exposure of a human being to ionizing radiation (low-LET).

We are aware that with the current study there are limitations that we tried to extend and provide more accurate and specific data on different exposure scenarios. We understand that it is difficult to cover all cases but the study is original and we hope that it will be well-appreciated by the radiation community and will provide a useful set of data for researchers worldwide to compare and use our results. Generally, our methodology has proved to be useful for assessing γ rays-induced DNA damage levels of the exposed population in the case of a REI and better understanding of the long-term health effects of exposure of the population to IR.

REVIEWER #3:

 

This is a very interesting article describing the results of DNA damage calculations. The results include the MCNP absorbed dose and the initial levels of SSBs and DSBs DNA damages calculated with the MCDS code. The interface data transfer from MCNP to MCDS is outlined. It includes a long list of literature. An introduction to the subject of the impact of radiation exposure and DNA damages is given to the full extent. That is a very useful overview, with an extensive literature list and background information.

The authors would like to thank the Reviewer for the time that he spent on reading and commenting creatively on our manuscript. All his comments have been taken into account by us, inspiring us to correct our oversights and mistakes and presenting a better manuscript to the reader. We really thank him/her.

 

Unfortunately, the caesium-137 source of radiation is defined not accurately, missing the component of electron radiation from caesium-137. The MCNP modeling of the radiation source should be described in more detail. Because depending on the source definition, MCNP calculates spectra (photon, electron cascades), nuclear reactions, and responses. Beta radiation of caesium-137 is a type of ionizing radiation, and the absence of such radiation from the source should be explicitly mentioned in the manuscript. In general, the presented results could be used by the scientific community if the authors define the modeling assumptions, particularly the MCNP source definition.

Response: These general comments by the Reviewer are answered in detail together with his specific comments as follows. See below.

 

Line 36: Please change “occur” to “occurs” in the sentence “Large-scale exposure to IR, in terms of both amount of radiation and number of exposed population occur rarely…”.

Corrected, see L.40

 

Line 114: Please remove the introducing phrase “On the other hand” because there are no contradictions or two opposite facts presented. Fact that iodine accumulates in the thyroid gland does not contradict the fact that strontium accumulates in bones. If you want to connect stylistically these facts, you can use the phrase "In addition".

Corrected, see L.118

 

Line 161: Please clarify what you assumed by “others” in the sentence “and others where the corresponding value is up to 50 mSv.” It is not clear from the context.

Corrected, see L.177

 

 

The caesium-137 radioactive source used in the MCNP transport calculations was not well defined. In lines 272-273 we read “an isotropically distributed cylindrical source of 137Cs has been placed in the ground, at a depth of 20 cm”. The size of the volumetric cylindrical source is defined in lines 286-288: “In our study we have considered an isotropic cylindrical source and therefore in our simulations we have planned its surface area (base of the cylinder) to be 1256 m2 (radius 20 m).” After that in lines 292-294 you mentioned: “In our study, the material surrounding the source of gamma rays (137Cs) includes all those elements contained in soil in the respective proportions (i.e. Si, Fe, Mg, K, Ca, O, Na, Al, Ti and Mn) considering a typical value of dry density ~1.52 g/cm3”. Figure 1 defines MC geometry model of the MCNP6.1 simulation including the source, the phantom and all the patterns used in the model. Radius of the “Source Volume” is 20 m. That means geometrically nothing surrounds the source. Please explain how you defined the source volume. How you defined the MCNP material composition for the cylindrical cell used as a volumetric source, did you mix caesium-137 radioactive isotope with the soil elements? This is important question because the source normalization is given by the caesium-137 surface activities 37, 555, 1480, and 3700 kBq/m2.

 

Response: The whole setting is as follows: the human phantom (depicted in Fig.1 as a thin cylinder) of 1,80 m height (radius 25 cm) stands in the middle of the outer cylinder (radius 20 m) filled with air (surrounding environment). The base cylinder (radius 20 m) represents the source volume on which the ‘human’ stands (i.e. the surrounding ground composed of soil and contaminated with the radionuclide ¹³⁷Cs in different surface activity values). As a whole, the radionuclide is considered mixed with the soil; the latter is composed (mass percentage) of:

 

            -          Si (z=14):   27.1183 %

-          Fe (z=26):   5.6283 %

-          Mg (z=12):  1.3303 %

-          K (z=19):   1.4327 %

-          Ca (z=20):   5.1167 %

-          O (z=8):     51.3713 %

-          Na (z=11):   0.614 %

-          Al (z= 13):  6.8563 %

-          Ti (z=22):   0.4605 %

-          Mn (z=25):  0.0716 %

 

In this material (its dry density is 0.00152 g/cm³) with the aforementioned composition are produced the γ-rays of ¹³⁷Cs (661.67 keV). We have added the relevant comments in the new manuscript (see L.310, L.317, L.319-323 & L. 353-361).

 

We infer that on the upper surface of the cylinder the caesium-137 surface activities 37, 555, 1480, and 3700 kBq/m2. If it is a surface source, then exclusion of the beta source of caesium-137 could be incorrect at least for the short distance from the caesium-137 contaminated surface. Beta radiation has a short range, which makes it harmful mostly if beta-radioactive material is swallowed or inhaled. However, even in a short distance, electrons can ionize the substance of the human phantom, it is a type of IR - ionizing radiation you have explored. In many places of the manuscript, you mentioned that you have defined only the gamma source. For example, in lines 504-506: “As expected, our results show that for a given exposure time and 137Cs surface activity, the absorbed dose decreases exponentially as a function of the height from the ground surface of the gamma-ray source.” You have explicitly calculated with the MCNP code the secondary electrons spectrum produced by emitted photons. This calculation was mentioned in preparation of the MCDC input data file in lines 338-339: “an input file (in which we set the calculated value of the absorbed dose by MCNP, as well as the energy spectrum of the secondary electrons down to 10 eV)”. If my conclusion is correct, please explicitly write in your manuscript something like this: “The caesium-137 beta decay source was not taken into account in the definition of the MCNP radiation source.” Particularly, the readers should be aware of such neglect of beta radiation from caesium-137 if your estimations of the carcinogenesis effects.

Response:  The Reviewer is right. In response, extensive additional simulations have been run. More specifically, we have calculated the secondary electrons spectrum produced by γ-rays through the MCNP6.1 code, which, we then have used as input data in the MCDS code for the assess of DNA damage. After the Reviewer’s comment, we ran the input files with the same geometry in the MCNP-CP code [10], which has the ability to calculate the corresponding beta decay spectrum; through the latter calculation we inferred that the range of the electrons emitted by ¹³⁷Cs during β decay in the soil towards the human phantom is only some μm.  It is true that in such calculations when there is a ‘contact’ geometry, as in this case, (the human phantom is in contact with the ground/stands on it) the omission of the beta radiation of ¹³⁷Cs is a great error which may lead to a serious underestimation of the dose. But, here, in our case, the source is very extended in space - in comparison to the phantom’ dimensions – and in a long distance from the standing ‘human’ - in comparison to the range of beta radiation – that the majority of these emitted electrons is absorbed in the intervening air, nearly never reaching the surface of the ‘human body’. The only component that reaches this ‘body’ is the very penetrating radiation of 661.67 keV by photons emitted from the ¹³⁷Cs. In practice, these photons are emitted with probability ~ 85%; in this way, while we consider an emission of these photons with probability 100% (as in the MCNP6.1) – ignoring other radiation components emitted by ¹³⁷Cs (such as x-rays with lower energy) – as a matter of fact we partially overestimate the deposited dose, and especially by ~ 17% (when we consider only photons of such an energy).     

Practically, we may get the same result by some simple mathematical operations. The average energy of the electrons emitted from ¹³⁷Cs during beta decay is by ~ 95% equal to 174.32 keV. Using the simple online ESTAR (NIST) code we may calculate the range of these electrons in dry air: it is equal to 0.04103 g/cm². If we divide this number by the air density (~ 0.001225 g/cm³) we find ~ 33.5 cm only maximum range of them in the air. If we consider their movement in soil, their range is really insignificant (only some μm).

At last, the component of beta radiation is very small due to the fact that our source is very extended in comparison to the phantom’s dimensions and since these particles are charged, they steadily lose energy. This means that the energy deposited by them on the ‘human body’ is really insignificant; so does the dose. We have commented on this in the new version of manuscript as suggested also by the reviewer (see L.364-379).

 

Lines 398-399: Please correct your exaggerated evaluation of the SSB and DSB breaks decrease presented in Figs.3a, b: “the number of the expected SSBs per cell for the deposition density of 3700kBq·m-2 tends to drop up to an order of magnitude”. Actually, as followed from Fig. 3b, the SSB/cell results drop from 1.5 to 0.6, which is a factor of 2.5 (1.5/0.6=2.5) decrease, certainly not an order of magnitude. Please correct your observations.

Response: Corrected, see L.455

 

 

References

1. Goorley, J.T. Initial mcnp6 release overview - mcnp6 version 1.0.
2. Nikjoo, H.; O'Neill, P.; Terrissol, M.; Goodhead, D.T. Modelling of radiation-induced DNA damage: The early physical and chemical event. International journal of radiation biology 1994, 66, 453-457.
3. Nikjoo, H.; O'Neill, P.; Goodhead, D.T.; Terrissol, M. Computational modelling of low-energy electron-induced DNA damage by early physical and chemical events. International journal of radiation biology 1997, 71, 467-483.
4. Friedland, W.; Dingfelder, M.; Jacob, P.; Paretzke, H.G. Calculated DNA double-strand break and fragmentation yields after irradiation with he ions. Radiation Physics and Chemistry 2005, 72, 279-286.
5. Semenenko, V.A.; Stewart, R.D. Fast monte carlo simulation of DNA damage formed by electrons and light ions. Phys Med Biol 2006, 51, 1693-1706.
6. Semenenko, V.A.; Stewart, R.D. A fast monte Carlo algorithm to simulate the spectrum of DNA damages formed by Ionizing Radiation, Radiation Research 2004, 161, 451-457.
7. Brenner DJ, Doll R, Goodhead DT, Hall EJ, Land CE, Little JB, Lubin JH, Preston DL, Preston RJ, Puskin JS, et al: Cancer risks attributable to low doses of ionizing radiation: Assessing what we really know. Proc Natl Acad Sci USA 2003, 100: 13761-13766,
8. Averbeck D. Does scientific evidence support a change from the LNT model for low-dose radiation risk extrapolation? Health Phys 2009, 97: 493‑504.
9. Averbeck D: Non-targeted effects as a paradigm breaking evidence. Mutat Res 2010, 687: 7-12.
10. Berlizov, A N, MCNP-CP: A Correlated Particle Radiation Source Extension of a General Purpose Monte Carlo N-Particle Transport Code, 2006, ACS Symposium Series 945:183-194.

Round 2

Reviewer 1 Report

The criticisms for the initial version of the manuscript was not sufficiently addressed. I suggest that the manuscript should be declined again.

Author Response

Dear Reviewer and Editor

We read with great dissapointment the reviewer's opinion. Although we respect it , we think it is from this point and beyond biased and not objective enough based on the fact that the revision was extensive and all logical comments and scientifically correct were addressed. The whole manuscript was supported with additional data and time consuming simulations and literature deposit and critical comparisons with published data. 

For example, the Reviewer insisted on the lack of significant insights into radiation science. 

But we all know that unfortunately, there are some unconnected gaps in our knowledge of the radiation effects in the cellular level till the later stages of the cell’s response and possible early stages of carcinogenesis. No one can argue this!

We have made a detailed response and major effort adding additional data accepting the fact that there are inherent limitations in this original study. 

We have stressed the facts that make our original and scientifcally correct.

We kindly ask the Reviewer to explain if possible where the revision has not addressed comments.

If the Reviewer does not respond although the great effort and revision made and coming from 3 well-known laboratories and groups then we ask for the Editor to make decision.

We will not revise the manuscript again based on judgments without specific explanations or justifications. 

Sincerely

Alex Georgakilas, PhD