Micronuclei in human peripheral blood lymphocytes exposed to mixed beams of X-rays and alpha particles

Staaf, Elina; Brehwens, Karl; Haghdoost, Siamak; Nievaart, Sander; Pachnerova-Brabcova, Katerina; Czub, Joanna; Braziewicz, J.; Wójcik, Andrzej

doi:10.1007/s00411-012-0417-x

Cited by 30 publications

(42 citation statements)

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“…This could be due to differences in the protocols and slide preparation methods employed. However, in our previous publication we observed similar levels of MN as in the present investigation [18]. …”

Section: Discussionsupporting

confidence: 90%

Possible benefits of tomato juice consumption: a pilot study on irradiated human lymphocytes from healthy donors

Nakamura

Itaki

Saito

et al. 2017

Nutr J

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BackgroundReactive oxygen species (ROS) mediate much of the DNA damage caused by ionizing radiation. Among carotenoids, lycopene and β-carotene, present in tomato juice, are known to be strong radical scavengers. The aim of the study was to investigate the effect of tomato juice intake on the levels of DNA damage and oxidative stress in human whole blood induced by in vitro exposure to X-rays.MethodsTen healthy adults were asked to drink 190 g of tomato juice, containing 17 mg lycopene and 0.25 mg β-carotene, per day for 3 weeks and then refrain from drinking it for 3 weeks. Peripheral whole blood samples were collected before and after the intake period of tomato juice and after the washout period. The blood samples were exposed in vitro to X-ray doses of 0, 0.1, 0.5, and 2 Gy. Cytogenetic damage was measured using the cytokinesis-block micronucleus (CBMN) assay and the dicentrics (DIC) assay. The level of oxidative stress was determined using serum 8-oxo-7, 8-dihydro-2-deoxyguanosine (8-oxo-dG) and plasma reactive oxygen metabolite-derived compounds (d-ROMs). The concentration of carotenoids in plasma was measured at the three time points.ResultsThe levels of 8-oxo-dG tended to decrease during the intake period and increase during the washout period. A non-significant inverse correlation was noted between the plasma concentration of lycopene plus β-carotene and the level of 8-oxo-dG (P = 0.064). The radiation-induced MN and DIC frequencies increased in a dose-dependent manner, and when compared at the same dose, the MN and DIC frequencies decreased during the intake period compared with those at baseline and then increased during the washout period. The results suggest that continuous tomato juice consumption non-significantly decreases extracellular 8-oxo-dG, d-ROMs, and MN. Tomato juice intake had minimal or no effect on radiation-induced 8-oxo-dG and d-ROMs. For most radiation doses, continuously tomato juice intake lowered the levels of MN and DIC.ConclusionTomato juice consumption may suppress human lymphocyte DNA damage caused by radiation, but further examination is required.Trial registration 2014-001 and 2014-R06.

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Section: Discussionsupporting

confidence: 90%

Possible benefits of tomato juice consumption: a pilot study on irradiated human lymphocytes from healthy donors

Nakamura

Itaki

Saito

et al. 2017

Nutr J

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“…The consequences of this delay are not clear, since 24 h after irradiation the levels of IRIF were similar for all irradiation schemes. However, it is worthwhile to note that our earlier study showed a higher than predicted level of micronuclei in mixed beam-exposed human peripheral blood lymphocytes [46]. There we also speculated that DNA repair is impaired in cells exposed to a mixed beam.…”

Section: Discussionmentioning

confidence: 62%

“…The rational for using these doses was that in our earlier study we saw a synergistic effect of mixed beams in this dose range [46]. For analysis of repair kinetics 0.27 Gy alpha particles, 0.8 Gy X-rays and 0.13 + 0.40 Gy mixed beams (of alpha particles and X-rays, respectively) were the chosen doses.…”

Section: Resultsmentioning

confidence: 99%

“…In the setups applied by us and Franken et al [50] one particle track could only be viewed as a singe IRIF, which led to an underestimation of the number of IRIF after alpha particles and thereby the RBE. Previously, alpha particle RBE values of 2.57 and 1.90 for 37% and 10% clonogenic survival in AA8 cells and 3.2 for micronuclei in human peripheral blood lymphocytes have been observed using this setup [45,46]. The dose response of mixed beam-irradiated cells was intermediate to that of X-ray and alpha particle-irradiated cells, and the differences in repair kinetics between observed and predicted for the first 3 time points were non-significant (Figure 2C-D).…”

Section: Discussionmentioning

confidence: 99%

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Gamma-H2AX foci in cells exposed to a mixed beam of X-rays and alpha particles

et al. 2012

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BackgroundLittle is known about the cellular effects of exposure to mixed beams of high and low linear energy transfer radiation. So far, the effects of combined exposures have mainly been assessed with clonogenic survival or cytogenetic methods, and the results are contradictory. The gamma-H2AX assay has up to now not been applied in this context, and it is a promising tool for investigating the early cellular response to mixed beam irradiation.PurposeTo determine the dose response and repair kinetics of gamma-H2AX ionizing radiation-induced foci in VH10 human fibroblasts exposed to mixed beams of 241Am alpha particles and X-rays.ResultsVH10 human fibroblasts were irradiated with each radiation type individually or both in combination at 37°C. Foci were scored for repair kinetics 0.5, 1, 3 and 24 h after irradiation (one dose per irradiation type), and for dose response at the 1 h time point. The dose response effect of mixed beam was additive, and the relative biological effectiveness for alpha particles (as compared to X-rays) was of 0.76 ± 0.52 for the total number of foci, and 2.54 ± 1.11 for large foci. The repair kinetics for total number of foci in cells exposed to mixed beam irradiation was intermediate to that of cells exposed to alpha particles and X-rays. However, for mixed beam-irradiated cells the frequency and area of large foci were initially lower than predicted and increased during the first 3 hours of repair (while the predicted number and area did not).ConclusionsThe repair kinetics of large foci after mixed beam exposure was significantly different from predicted based on the effect of the single dose components. The formation of large foci was delayed and they did not reach their maximum area until 1 h after irradiation. We hypothesize that the presence of low X-ray-induced damage engages the DNA repair machinery leading to a delayed DNA damage response to the more complex DNA damage induced by alpha particles.

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“…IR-induced clustered damage two of the donors. The study is a continuation of our analyses of cellular effects of simultaneous exposure to alpha radiation and X-rays [18,[20][21][22][23]].…”

Section: Introductionmentioning

confidence: 99%

Impact of ATM and DNA-PK Inhibition on Gene Expression and Individual Response of Human Lymphocytes to Mixed Beams of Alpha Particles and X-Rays

Cheng

Brzozowska

Lisowska

et al. 2019

Cancers

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Accumulating evidence suggests a synergistic effect in cells simultaneously exposed to different types of clustered and dispersed DNA damage. We aimed to analyse the effect of mixed beams of alpha particles and X-rays (1:1 dose of each) on DNA damage response genes in human peripheral blood lymphocytes isolated from four donors. Two donors were compared upon inhibition of ATM or DNA-PK and at different sampling times. qPCR was used to measure mRNA levels of FDXR, GADD45A, BBC3, MDM2, CDKN1A, and XPC 24 h following exposure. Generally, alpha particles and mixed beams were stronger inducers of gene expression compared to X-rays, displaying saturated versus linear dose-response curves, respectively. Three out of four donors responded synergistically to mixed beams. When two donors were sampled again one year later, the former additive effect in one donor was now synergistic and no significant difference in intrinsic radiosensitivity was displayed, as determined by gamma-radiation-induced micronuclei. ATM, but not DNA-PK inhibition, reduced the radiation-induced gene expression, but differently for alpha radiation between the two donors. In conclusion, synergy was present for all donors, but the results suggest individual variability in the response to mixed beams, most likely due to lifestyle changes.

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Micronuclei in human peripheral blood lymphocytes exposed to mixed beams of X-rays and alpha particles

Cited by 30 publications

References 61 publications

Possible benefits of tomato juice consumption: a pilot study on irradiated human lymphocytes from healthy donors

Possible benefits of tomato juice consumption: a pilot study on irradiated human lymphocytes from healthy donors

Gamma-H2AX foci in cells exposed to a mixed beam of X-rays and alpha particles

Impact of ATM and DNA-PK Inhibition on Gene Expression and Individual Response of Human Lymphocytes to Mixed Beams of Alpha Particles and X-Rays

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