Iodine-125, a tracer in cell biology: physical properties and biological aspects

Ertl, H.H.; Feinendegen, L. E.; Heiniger, H J

doi:10.1088/0031-9155/15/3/005

Cited by 100 publications

(39 citation statements)

References 22 publications

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“…Furthermore, the results of the DFT calculations explain the experimentally observed film stability. The calculated I-Au and Te-Au binding energies, 2.1 eV and 3.1 eV respectively, are much larger than the nuclear recoil energy (< 0.1 eV), thus preventing rupture of the surface bonds following decay 18 . More importantly, there is also substantial hybridization of the I/Te valence orbitals with the Au surface which we postulate imparts resilience against Coulomb explosion by allowing fast electron transfer from the Au surface that rapidly neutralizes the atom undergoing decay 15,23 .…”

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confidence: 84%

“…Therefore, a major challenge in realizing a nano-structured radiation source is the design of a system that is robust under the ultra-fast release of energy and particles that accompany each atomic decay event. In anticipation of this challenge we have chosen 125 I/Au for this work, because the wellknown, robust I/Au chemistry makes this system a good candidate for a stable 2-D emitter 18,19 . Samples were prepared using an ambient drop-casting method adapted from the previous (non-radioactive) .…”

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“…Theoretical studies have indicated that the decay of condensed phase 125 I leads to an average total energy of 18.3 keV being deposited into its surroundings in the form of hot electrons 3,22 . When using the traditional convention of only considering total deposited energy, it would be reasonable to suspect film damage via local atomic desorption in 125 I films 18 . However this is not what we observe; when imaging 100 × 100 nm The striking resilience of the radioactive film can be explained by the density functional theory calculations (DFT) we performed for various I, Te and mixed I/Te overlayers.…”

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Enhancement of low-energy electron emission in 2D radioactive films

et al. 2015

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High-energy radiation has been utilized for decades, however, the role of low-energy electrons created during irradiation has only recently begun to be appreciated Nuclear decay is one of the most extreme processes and is central to a range of fields including energy, medicine, imaging, labelling, archaeology and sensing. Radiation in the form of alpha particles, beta particles and gamma rays have fundamentally different interactions with matter and therefore exhibit different mean-free paths (∼1 μm, 1 mm and 1 cm, respectively). These forms of primary radiation deposit their energy over the course of their trajectory by ionizing their surroundings and producing non-thermal secondary electrons. Only very recently has the ability of low-energy secondary electrons to induce chemical reactions and biological damage begun to be appreciated 1 , because they have energies below the typical ionization threshold of organic matter. For example, low-energy electrons (3-20 eV) have been shown to be effective at causing DNA cleavage 2,4,7 . This ability stems from their high cross-section for breaking chemical bonds, and as a consequence they have a very short meanfree path of ∼1-10 nm in solution 8,9 . Furthermore, hot electrons that are not captured by surrounding molecules become thermalized as solvated electrons which are known to be chemically and biological active [9][10][11][12] . To harness these unique properties, the design of radioactive materials that increase and localize the flux of short-range lowenergy electrons to target sites is crucial for their application in targeted cancer therapies that minimize damage to healthy cells. Thus far, it has not been possible to design atomically precise radioactive materials that maximize these effects due to self-destruction arising from nuclear recoil, Coulomb explosion and self-irradiation [13][14][15][16] . We report a straightforward method for synthesizing monolayer films of radioactive 125 I atoms on gold-coated mica substrates under ambient conditions, and characterize their composition and their electron emission. Despite being synthesized from radioactive 125 I (> 99.9% purity) they are robust with respect to self-destruction, and provide well-defined, intense planar sources of secondary electrons. 125I decays by electron capture (EC) of a core shell electron to produce a nuclear excited state of 125 Te (Figure 1a), the majority of which eject another core

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Enhancement of low-energy electron emission in 2D radioactive films

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“…The scatter of electrons from 125I decay has been calculated by Ertl et al (11) and compared to that of 'H. Over 55% of the grains observed in film should be no further from the source of radiation than grains obtained after 'H decay, i.e., within a radius of 0.5 Mm of the source.…”

Section: Specific Activity and Degree Of Iodination Of [125i]rnamentioning

confidence: 99%

The Use of Iodinated RNA for Gene Localization

Prensky¹,

Steffensen²,

Hughes³

1973

Proc. Natl. Acad. Sci. U.S.A.

104

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Carrier-free iodination of 5S RNA with 1261 yields a probe suitable for use in cytological RNA-DNA hybridization studies. The genes coding for 5S ribosomal RNA in Drosophila could be localized by autoradiography after a 2-day exposure, whereas a 2-month exposure is needed when the best available ['H]RNA is used. The procedure introduces one covalently bound 12"I atom per 100 nucleotides, resulting in a specific activity of over 108 dpm/,ug of RNA. The method may be readily applied to other problems involving molecular hybridization techniques.Molecular hybridization of radioactive RNA or DNA to chromosomes offers the opportunity for localizing genes or specific DNA sequences by autoradiography. One needs to isolate in high purity a specific gene product that is either labeled or can be used as a template to transcribe a labeled probe; the probe must have specific activity high enough to yield a detectable number of disintegrations at the site where it hybridizes; there must be a sufficient number of complementary nucleotides in one region of the chromosome to bind detectable amounts of the probe. The higher the specific activity of the probe, the smaller is the template that may be detected.Molecular hybridization in situ has been successfully applied to diploid cells that contain repeated large DNA sequences (1-5) or highly amplified specific genes during specific times of cell development (6). Localization of smaller sequences that are not highly redundant has been successful only in giant chromosome preparation of some dipterans (7, 8); identification of hybridized regions required months of autoradiographic exposure to obtain convincing numbers of silver grains.All successful gene localizations have been obtained with 'H-labeled RNA or DNA. The main requirement for direct chemical labeling of isolated RNA is that sufficient label be introduced into the RNA without loss of its ability to hybridize specifically with its template. The labeling isotope should have a reasonably short half-life since the maximal specific activity of an isotope is inversely related to its halflife. We have chosen to work with 125I, which has a 60-day half-life, 1/70th that of 3H. Commerford (9) has developed mild conditions for iodinating nucleic acids. He showed that the iodinated nucleic-acid product contained iodine almost exclusively at the C5 position on cytosine, and that DNA containing 10% substitution of iodine in cytosine preserved Abbreviation: SSC, 0.15 M NaCl-0.015 M Na citrate.

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“…However, there has been no attempt to relate the microscopic distribution of energy to the efficacy of various internal emitters in producing cell transformation, despite the repeated demonstration that the potential for cell killing strongly depends upon this distribution (9-11). This is particularly evident in comparing the effects of "2I with 3H; 1251 is much more cytotoxic than 3H and produces proportionally more chromosomal aberrations (11).The relatively high lethality of "2I generally is ascribed to its release of an extremely localized burst of low-energy Auger and Coster-Kronig electrons upon decay (12). Thus, it is an efficient inducer of DNA double-strand breaks when incorporated into the DNA structure (13).…”

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Malignant transformation induced by incorporated radionuclides in BALB/3T3 mouse embryo fibroblasts.

LeMotte¹,

Adelstein²,

Little³

1982

Proc. Natl. Acad. Sci. U.S.A.

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The induction of lethality and malignant transformation by 5-["'5I]iododeoxyuridine and [3H]thymidine incorporated into cellular DNA and by x-irradiation was studied in vitro in BALB/3T3 cells. Under these conditions, 125I radiation is highly localized to small regions of the DNA at the site of each decay and produces DNA double-strand breaks with high efficiency. Incorporated 1251 was found to be 12-16 times as lethal per decay as incorporated 3H. For the induction of malignant transformation, however, 1251 was approximately 25 times as effective per decay as 3H. When the frequencies of transformation induced at various levels ofsurvival by 125I, 3H, and x-rays were compared, lethality was found to correlate closely with transformation at doses that yielded significant cell killing. An exception occurred at low doses, where 125I appeared much more efficient than x-irradiation in inducing transformation; transformation frequencies equal to those induced by 3-5 Gy of x-rays resulted from '251 exposures that yielded little or no cell killing.Ionizing radiation is capable of inducing the malignant transformation of cells in animals and humans (1,2). This has been demonstrated for both external radiation and internal emitters. There also have been a number of reports describing the carcinogenic effects of other f3-and a-particle-emitting radionuclides in animals and man (2).In vitro assays also have been used to study mammalian cell transformation by external radiation, especially x-rays, and by chemical carcinogens (4-8). However, there has been no attempt to relate the microscopic distribution of energy to the efficacy of various internal emitters in producing cell transformation, despite the repeated demonstration that the potential for cell killing strongly depends upon this distribution (9-11). This is particularly evident in comparing the effects of "2I with 3H; 1251 is much more cytotoxic than 3H and produces proportionally more chromosomal aberrations (11).The relatively high lethality of "2I generally is ascribed to its release of an extremely localized burst of low-energy Auger and Coster-Kronig electrons upon decay (12). Thus, it is an efficient inducer of DNA double-strand breaks when incorporated into the DNA structure (13). The '2Te nucleus of high positive charge that results from the decay of 1"I also may contribute to localized molecular damage (14). On the other hand, decay of 3H incorporated into DNA generally has been shown to produce effects similar to low LET radiations (15).In this report, we show that "2I incorporated into DNA as 5-['2I]iododeoxyuridine ('"IdUrd) is considerably more efficient than 3H in inducing cell transformations. Moreover, when compared at equal levels of cytotoxicity with both external xrays and 3H, 125I produces a greater transformation frequency at high survival fractions. This differential effect suggests that at low doses, Auger electron-emitters localized to the genome may have malignant consequences far greater than expected from their lethal properties. ...

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Iodine-125, a tracer in cell biology: physical properties and biological aspects

Cited by 100 publications

References 22 publications

Enhancement of low-energy electron emission in 2D radioactive films

Enhancement of low-energy electron emission in 2D radioactive films

The Use of Iodinated RNA for Gene Localization

Malignant transformation induced by incorporated radionuclides in BALB/3T3 mouse embryo fibroblasts.

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