The Question of Relative Biological Effectiveness and Quality Factor for Auger Emitters Incorporated into Proliferating Mammalian Cells

Howell, Roger W.; Rao, Dandamudi V.; Hou, De‐Yan; Narra, Venkat; Sastry, K.S.R.

doi:10.2307/3578051

Cited by 69 publications

(87 citation statements)

References 27 publications

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“…Therefore, particular attention must be paid to the selection of the reference radiation (5,10,16,30). In our earlier work using the same experimental model, the effects of a variety of sources of low-LET radiation were examined including external X rays (8) and intratesticularly administered β-particle and γ-ray emitters (8,16,24).…”

Section: Relative Biological Effectiveness As a Function Of Alpha-parmentioning

confidence: 99%

Radiotoxicity of Gadolinium-148 and Radium-223 in Mouse Testes: Relative Biological Effectiveness of Alpha-Particle Emitters In Vivo

Howell

Goddu²,

Narra³

et al. 1997

Radiation Research

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The biological effects of radionuclides that emit α particles are of considerable interest in view of their potential for therapy and their presence in the environment. The present work is a continuation of our ongoing effort to study the radiotoxicity of α-particle emitters in vivo using the survival of murine testicular sperm heads as the biological end point. Specifically, the relative biological effectiveness (RBE) of very low-energy α particles (3.2 MeV) emitted by 148 Gd is investigated and determined to be 7.4 ± 2.4 when compared to the effects of acute external 120 kVp X rays. This datum, in conjunction with our earlier results for 210 Po and 212 Pb in equilibrium with its daughters, is used to revise and extend the range of validity of our previous RBE-energy relationship for α particles emitted by tissue-incorporated radionuclides. The new empirical relationship is given by RBE α = 9.14 − 0.510 E α , where 3 < E α < 9 MeV. The validity of this empirical relationship is tested by determining the RBE of the prolific α-particle emitter 223 Ra (in equilibrium with its daughters) experimentally in the same biological model and comparing the value obtained experimentally with the predicted value. The resulting RBE values are 5.4 ± 0.9 and 5.6, respectively. This close agreement strongly supports the adequacy of the empirical RBE-E α relationship to predict the biological effects of α-particle emitters in Vivo.

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Section: Relative Biological Effectiveness As a Function Of Alpha-parmentioning

confidence: 99%

Radiotoxicity of Gadolinium-148 and Radium-223 in Mouse Testes: Relative Biological Effectiveness of Alpha-Particle Emitters In Vivo

Howell

Goddu²,

Narra³

et al. 1997

Radiation Research

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“…To further characterize the nature of the radiobiological damage, the capacity of various radioprotectors to mitigate the lethal effects of these different radionuclides was measured and reported as a dose modifying factor (DMF). The highest DMFs were observed for tritiated water thereby suggesting that, as for other low-LET radiations, indirect effects are the predominant mechanisms of radiationinduced damage (Bishayee et al, 2000;Howell et al, 1991;Howell et al, 1998). Bystander effects are biological changes observed in cells in the vicinity of irradiated cells but that were not directly irradiated themselves.…”

Section: Human Health and Tritium In Drinking Watermentioning

confidence: 99%

Human Health and the Biological Effects of Tritium in Drinking Water: Prudent Policy through Science – Addressing the ODWAC New Recommendation

et al. 2011

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ᮀ Tritium is a radioactive form of hydrogen and is a by-product of energy production in Canadian Deuterium Uranium (CANDU) reactors. The release of this radioisotope into the environment is carefully managed at CANDU facilities in order to minimize radiation exposure to the public. However, under some circumstances, small accidental releases to the environment can occur. The radiation doses to humans and non-human biota from these releases are low and orders of magnitude less than doses received from naturally occurring radioisotopes or from manmade activities, such as medical imaging and air travel. There is however a renewed interest in the biological consequences of low dose tritium exposures and a new limit for tritium levels in Ontario drinking water has been proposed. The Ontario Drinking Water Advisory Council (ODWAC) issued a formal report in May 2009 in response to a request by the Minister of the Environment, concluding that the Ontario Drinking Water Quality Standard for tritium should be revised from the current 7,000 Bq/L level to a new, lower 20 Bq/L level. In response to this recommendation, an international scientific symposium was held at McMaster University to address the issues surrounding this change in direction and the validity of a new policy. Scientists, regulators, government officials, and industrial stakeholders were present to discuss the potential health risks associated with low level radiation exposure from tritium. The regulatory, economic, and social implications of the new proposed limit were also considered.The new recommendation assumed a linear-no-threshold model to calculate carcinogenic risk associated with tritium exposure, and considered tritium as a non-threshold chemical carcinogen. Both of these assumptions are highly controversial given that recent research suggests that low dose exposures have thresholds below which there are no observable detrimental effects. Furthermore, mutagenic and carcinogenic risk calculated from tritium exposure at 20 Bq/L would be orders of magnitude less than that from exposure to natural background sources of radiation. The new proposed standard would set the radiation dose limit for drinking water to 0.0003 mSv/year, which is equivalent to approximately three times the dose from naturally occurring tritium in drinking water. This new standard is incongruent with national and international standards for safe levels of radiation exposure, currently set at 1 mSv/year for the general public. Scientific research from leading authorities on the carcinogenic health effects of tritium exposure supports the notion that the current standard of 7,000 Bq/L (annual dose of 0.1 mSv) is a safe standard for human health.*Authors contributed equally to the writing and preparation of this manuscript. Address correspondence to D.R. Boreham, Department of Medical Physics and Applied Radiation Sciences, McMaster University, Hamilton, ON, CAN, L8S 4K1; Email: boreham@mcmaster.ca Policy-making for the purpose of regulating tritium levels in drinking water is a ...

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“…About 72% of this radiochemical localizes in the cytoplasm and 28% in the nucleus (38). Figure 1 shows the surviving fraction of cells in the multicellular cluster as a function of the cluster dose when 1%, 10%, 100% of the cells were radiolabeled.…”

Section: Nonuniform Distributions Of 210 Pomentioning

confidence: 99%

Challenges and progress in predicting biological responses to incorporated radioactivity

Howell¹,

Neti²,

Pinto³

et al. 2006

Radiation Protection Dosimetry

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Prediction of risks and therapeutic outcome in nuclear medicine largely rely on calculation of the absorbed dose. Absorbed dose specification is complex due to the wide variety of radiations emitted, nonuniform activity distribution, biokinetics, etc. Conventional organ absorbed dose estimates assumed that radioactivity is distributed uniformly throughout the organ. However, there have been dramatic improvements in dosimetry models that reflect the substructure of organs as well as tissue elements within them. These models rely on improved nuclear medicine imaging capabilities that facilitate determination of activity within voxels that represent tissue elements of about 0.2 -1 cm 3 . However, even these improved approaches assume that all cells within the tissue element receive the same dose. The tissue element may be comprised of a variety of cells having different radiosensitivities and different incorporated radioactivity. Furthermore, the extent to which nonuniform distributions of radioactivity within a small tissue element impact the absorbed dose distribution is strongly dependent on the number, type, and energy of the radiations emitted by the radionuclide. It is also necessary to know whether the dose to a given cell arises from radioactive decays within itself (self-dose) or decays in surrounding cells (cross-dose). Cellular response to selfdose can be considerably different than its response to cross-dose from the same radiopharmaceutical. Bystander effects can also play a role in the response. Evidence shows that even under conditions of "uniform" distribution of radioactivity, a combination of organ dosimetry, voxel dosimetry and dosimetry at the cellular and multicellular levels can be required to predict response.

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The Question of Relative Biological Effectiveness and Quality Factor for Auger Emitters Incorporated into Proliferating Mammalian Cells

Cited by 69 publications

References 27 publications

Radiotoxicity of Gadolinium-148 and Radium-223 in Mouse Testes: Relative Biological Effectiveness of Alpha-Particle Emitters In Vivo

Radiotoxicity of Gadolinium-148 and Radium-223 in Mouse Testes: Relative Biological Effectiveness of Alpha-Particle Emitters In Vivo

Human Health and the Biological Effects of Tritium in Drinking Water: Prudent Policy through Science – Addressing the ODWAC New Recommendation

Challenges and progress in predicting biological responses to incorporated radioactivity

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