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Do the biological effects of Uranium result from secondary photoelectron amplification of background radiation? Part I: Particles

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Busby, Chris; University of Liverpool, Human anatomy and Cell biology; Green Audit, Research radiation biophysics < Cross-disciplinary subjects < BIOLOGY uranium, radiation, photoelectron, cancer, heavy metals, X-ray

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Do the biological effects of Uranium result from secondary photoelectron amplification of background radiation? Part I: Particles

Chris Busby Dept. Human Anatomy and Cell Biology, University of Liverpool Green Audit, Castle Cottage, Sea View Place, Aberystwyth SY231DZ christo@liv.ac.uk

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Abstract

Biological effects of ionising radiation are mediated through reactive species by interaction between secondary electrons and the genetic components of tissue, mainly chromosomal DNA. Conventional risk models (e.g. of the International Commission on Radiological Protection, ICRP) concede the importance of ionisation density at the target through a system of weighting of the quantity absorbed dose. These weightings are not yet extended to all other situations of high ionisation density e.g. DNA bound Auger emitters even though these are known to carry enhancement of risk relative to their averaged dose. However, an interesting radiological situation arises in the case of internal micro- and nano-particles of elements of high atomic number since the absorption of gamma radiation is roughly proportional to the fourth power of the atomic number. Gamma absorption for photon energies below 250keV (e.g. in natural background radiation) can be enhanced by large factors through creation of short range and highly ionising photoelectrons. In this, the first of two contributions on this issue I discuss the theoretical enhancements from Uranium (Z=92) particles and show that they are optimum

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for sub-micron sized particles since for larger diameters there is self absorption of energy. I draw attention to work that shows that these particle photoelectron enhancements exist: they have been recently reported by researchers attempting to use gold particles to enhance radiotherapy. I suggest that they may be the origin of some hitherto inexplicable effects which go beyond uranium genotoxicity.

Key Words: uranium, depleted uranium, photoelectrons, enhancement, cancer, genetic damage, heavy metals, particles, radiation, gamma ray, X-ray.

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Introduction

There has been a revival of interest in the health effects of internal exposure to uranium driven by concerns about the health of those exposed to depleted uranium (DU) aerosols. The Royal Society (RS) reported on the radiological and chemical risks of DU, arguing in both cases that at levels of exposure likely to be experienced by troops and civilians, there seemed little cause for concern (Royal Society 2001, 2002). Nevertheless, even at the time there were anecdotal reports of ill health among veterans and also data which showed high levels of chromosome aberration in veterans with measured uranium in urine (Schroeder et al, 2003). The conventional radiobiological risk methodology employed by RS2001, the averaging Absorbed Dose methods of the International Commission on Radiological Protection are increasingly being questioned regarding their validity for internal exposures to anisotropic sources (ECRR2003, CERRIE 2004a, 2004b, IRSN 2005). Reports of anomalous uranium and uranium particle effects in

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humans are increasingly seen but always include effects (heritable defects, cancer, leukaemia) which seem to be those expected from radiation exposure but at exposure levels that which would be unpredicted on the basis of the intrinsic radioactivity of uranium (e.g. Bertell (2006), Hindin et al 2005, Craft et al 2004, Schroeder et al 2003, Abu-Qare and Abou Donia 2002, Durakovic 1999, Zaire et al, 1997). Uranium is a weak alpha-emitter and, in secular equilibrium with its two daughter products Thorium 234 and Protoactinium 234m, has a combined activity of about 36MBq/Kg. Absorbed doses from levels of uranium likely to be found in individuals exposed to a few milligrams of Depleted Uranium dust by inhalation are microSieverts, far too low (on the basis of classic Joules Per Kilogram Absorbed Dose calculations) to be responsible for any measurable effects, as many authors to pointed out (e.g. Wakeford 2001, Mould 2001, Sztajnkrycer and Otten 2004). However, there have been a number of objective scientific studies which do show that Uranium exposure, both to particles and to ionic forms of Uranium, causes mutagenic and genomic effects not predicted from its activity. These have therefore been assumed to follow from some unelaborated chemical heavy metal effect or else some hypothetical synergy between radiation and chemistry. A series of studies by Miller et al make this clear (Miller et al 1998, 2000, 2001, 2002a, 2002b, 2004, 2005, 2007, Kalinich 2005) but others also have noted anomalous effects (Coryell and Stearns 2006, Wise et al 2007). Following these reports, Baverstock (2005) called for a re-consideration of the health effects of DU as did some members of the UK Depleted Uranium Oversight Board (DUOB 2007).

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It has been clear throughout the last fifty years that it is not Absorbed Dose but ionisation density at or near the DNA that drives mutation, genomic effects and hence risk (Gracheva and Korolev 1980, CERRIE 2004a, 2004b, ECRR2003). The effects found using Auger emitters bound to DNA show this (Kassis et al 1988, Sastry et al 1988). Therefore we would expect to see enhancement of radiation damage to cells if radioactive beta or alpha decays occurred in elements bound to the DNA (CERRIE 2004b, ECRR2003) but this is not the argument of the present contribution. What has been overlooked is the potential for radiological harm resulting from the increased absorption of natural background gamma radiation due to the high atomic number of uranium. For small particles, this radiation is re-emitted as short range photoelectrons and it is the local ionisation density enhancements from these I address here. There is another effect which is of interest in relation to the Auger findings. Since the chemical affinity of Uranyl ion UO2++ for DNA phosphate is very great, the high absorption of gamma rays and X-ray photons by DNA bound uranium atoms is also of interest: I examine these binding enhancements, which have wider significance elsewhere

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Photoelectron production by Gamma and X-rays

Gamma and X-rays interact with matter primarily through the photoelectric effect, Compton scattering and pair production. In the photoelectric effect, photons are absorbed by atoms and photoelectrons are released with energy equal to the difference between the incident photon energies and the electron binding energies. The probability for photoelectric conversion is difficult to calculate exactly but from

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experimental work a number of features are known: It is most significant for low energy photons below 200keV It increases rapidly as the fourth power of the atomic number, Z4. It increases rapidly with decreasing photon energy, roughly as EO3. There are discontinuities at energies corresponding to the binding energies of particular shells.

Calculations of absorbed dose from ambient photon fields assume energy absorbance essentially based on water. Now, the mean annual external doses from all external sources, averaged over all photon energies is usually given as between 1 and 2 mGy. The physical laws of absorption of gamma and X-ray photons by matter have the same form as Lamberts law, that is to say, for monochromatic photons intensity I0:

The linear absorption coefficient is a constant for a given absorber material and gamma ray photon energy. It is, however dependent on the state of the absorber or number of atoms per cubic centimetre. The mass attenuation coefficient m is independent of the state of the absorber material and is defined as = mQ where Q is its density. m also decreases with photon energy, sharply below 50keV. Values of the absorption coefficients have been measured for most materials and appropriate half-depths for penetration are also known. The relationship between the mass attenuation coefficients at various photon energy for Uranium-138 and skeletal muscle is given in Table1.

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<TABLE 1 HERE>

Below 200keV and for elements of high atomic number i.e. above about 30, almost all the absorbed energy is converted into photoelectrons. This is not entirely true above energies greater than 50 keV where there are some losses due to radiative effects which result in some loss of energy to e.g. fluorescence. Use of the photon mass absorption coefficient overcomes these problems and values for these are given in brackets where they are different from the attenuation coefficients. It follows that for exposures to energies below 200keV there is a conversion of incident gamma radiation into photoelectrons between 200 and 1500 times more effective for Uranium than tissue. What about Uranium oxide? By comparison with published data on Calcium and its salts, it would seem that the attenuation/energy relationship will be displaced by the ratio of densities of Uranium and the oxide. Thus the factors in Column 5 of Table 1 may be multiplied by 0.52. This gives a differential absorption of photons of between 200 and 1000 between uranium oxide particles and living tissue.

The range of photoelectrons in metal and in tissue.

Electrons interact through Coulomb scattering from atomic electrons. They may travel at relativistic speeds but will suffer large deflection is collisions and will therefore follow erratic paths. A relationship for the energy loss per unit path length of electrons was obtained by Bethe in 1930 but because of the random nature of the path the calculation of range is difficult, and so empirical data from monoenergetic electron beams must be

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used. It turns out that variation with the type of absorber is small, and so it is possible to obtain values for the range of electrons in tissue and in Uranium and Uranium Oxide for electrons of different energies. Some values are given in Table 2. Ranges in Table 2 may be compared with photon ranges for similar energy photons calculated from the absorption coefficients given in Table 1. These are given in Table 3 where the 75% absorption ranges are calculated from the coefficients. From these considerations it is possible to propose two effects:

1. That dense metal particles of high atomic number material will convert penetrating incident photon fields of between 20 and 200keV into short range photoelectrons some orders of magnitude more effectively than an equivalent volume of tissue. The initial energy of the photoelectrons will be equal to the photon energy less the binding energy of the electrons but this is a second order consideration: we can effectively assume no energy loss in this process. The effects will occur strongly for metals and dense metal oxide particles which are environmental contaminants for example Uranium oxide (DUO). The effect should occur for non-radioactive metal particles of moderate biological half-life trapped in tissue e.g. platinum from catalysers, nickel from refineries, gold from prostheses, tungsten etc. There will be a significant increase in the ionization density close to the particle caused by the presence of photoelectrons, particularly those with low energy since photon absorption from within the particle will produce electrons and X-rays that will lose energy on escaping.

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2. The efficiency of this focusing effect of external background gamma, and the lower energy re-scattered Compton radiation will decrease as the particle size increases. This is because internally generated photoelectrons themselves are absorbed by the material of the particle. Table 2 shows approximate relationship between range and energy for photoelectrons in Uranium and its oxide. Only the smaller particles below a few microns will significantly contribute to the effect which will be marginal for massive pieces of metal. Table 1 shows the range of photoelectrons of various energies in DU and in water. For photoelectron energies below 100keV, particle diameters greater than 5 diameter will represent the threshold for the internal absorption of a significant fraction of photoelectrons. On the other hand, ionization density of slow electrons in tissue near the surface of such a particle should be large, owing to the emergence of photoelectrons whose energy has been lost through collision inside the matrix of the particle.

There are two other relevant considerations: the energy spectrum of the natural background photon field and the variation in overall dose from this effect due to the relation between the number of particles and particle size at constant contamination

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levels.

The photon energy dispersion of the natural radiation field. In the external gamma field, the intensity rises sharply with decreasing energy. Fig1 shows a spectrum obtained with a NaI(Tl) detector near Bristol in 2002. The dispersion is a consequence of the splitting of incident energy by Compton and other track splitting

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effects. It is easy to show that the increase in density of ionization falls with energy in proportion to the inverse of the power of the mean number of track splitting events occurring at each cascaded reduction in energy. For simple reduction of energy by sequential binomial splitting e.g. balanced Compton photon and electron we would predict an increase in radiation energy proportional to E-2. Integration of the count rate per channel in the Thallium (Z = 81) doped Sodium Iodide crystal shows this effect. Over the energy spectrum about 50% of the total counts lie below 200keV, 38% between 200 and 500keV and only 12% above 500keV. Thus we are exposed mainly to low energy photons and of these, the skew is strongly to lower energies as predicted by the E-2 relationship. Fully a third of overall absorption is due to photons with energies below 100keV and a quarter of the dose is due to photons with energies below 50keV The mean natural background gamma dose is measured by tissue equivalent proportional counters as between 20-100nGy/hr in most areas of the UK. This gives 0.175-0.9 mSv per annum due to the external gamma background. These photons are sufficiently penetrating to pass through tissue but will nevertheless be absorbed by metal oxide particles to a high degree. For particles smaller than a few microns diameter, the energy will be quantitatively converted to photoelectrons. In other words, since the mean absorption of gamma photons of 50keV is about 500 times more likely for DU than tissue, the dose to the particle in the 20-100nGy/hr natural background field (allowing for the fraction of the field in this range) will be between 2500 and 12,000nGy/hr (22 and 110mSv per annum). This enhanced dose will occur close to the particles. Extra energy will be converted into photoelectrons with ranges up to 25 microns (Table 2) for particles of diameter less than 5 microns and various shorter ranges for larger particles up to about

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10 microns. The ionisation density will increase rapidly near the surface of the metal particle due to loss of energy in photoelectrons generated within the mass of the particle. Although this should be amenable to experimental measurement, we can make some calculations based on DU particles of different diameters and the conversion of incident photons of various energies and examine the ionization range relationship of the conversion process. There are three variables involved: particle diameter, incident gamma energy and position within the particle where the decay occurs to obtain the spectrum of energy distribution in the tissue close to the particle. Because the photoelectron can move in any direction from its origin, the problem is mathematically intransigent. If we reduce its complexity by assuming that radiologically relevant decays occur in the surface layer of the metal particle of depth equal to equal to half the photoelectron range it is possible to develop a relationship between particle size and the efficiency of the effect. The conclusion we draw with regard to the natural background gamma field is that it is mostly composed of low energy photons, and so will be absorbed by metal particles of high Z in which it will induce low energy photoelectrons which will cause dense ionisation in

tissue close to the particle.

Evidence for the existence of these effects

This enhancement of ionising radiation in tissue is not a new idea: it was first examined by Spiers (1949). Enhanced fields near gold prostheses were investigated by Castillo et al 1988 and photoelectron fields near a thin gold foil were measured by Regulla et al (1998) who found enhancements of 100- fold near the foil. Others tried to harness the effect for radiotherapy by use iodine contrast media and iodine itself (Z = 53) (Holt Rose et al

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1999, Santos Mello et al 1983, Mastsudeira, 1980). Interestingly, gold particles (Z=79) have also been investigated (Herold, 2000, Hainfeld et al, 2004). The latter study by Hainfeld et al forms the basis of a patent (US Patent 6955639B2) for enhancing radiotherapy using gold nanoparticles . In Hainfeld et al 2005, the enhancement of effect from gold nanoparticles injected into a mouse given subsequent X-ray radiotherapy for mammary tumours resulted in an astounding degree of success with 86% of animals surviving cancer relative to some 25% in the absence of the gold. One other interesting piece of supporting data is the discovery of tungsten particles in the atmosphere of Fallon, Nevada where there is a much discussed childhood leukaemia cluster (Sheppard et al 2007). The considerations outlined in this contribution would, of course, predict a significant photoelectron enhancement of dose from Tungsten (Z = 74). Kalinich et al, 2005 actually succeeded in inducing cancer in rats in which tungsten particles had been embedded. The idea that uranium particles (or uranium atoms bound to DNA) amplify effects from external irradiation can easily be investigated experimentally.

Finally, I point out that this contribution examines particles of high atomic number. In a separate paper I address these effects in elements of high atomic number, like Uranium, which have high affinity for DNA. It may be of relevance to these ideas, and I will elaborate on this, that no evolved biological systems employ elements of atomic number above Iron (Z = 26) and small amounts of first row Transition series elements with the unusual exception of Iodine (Z = 53), an element associated with metabolic control mechanisms and up-regulation of several specific genes, which I speculate may be associated with DNA repair systems. The two most radiation sensitive

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organs are those which contain these two elements: the blood forming system (leukemia) and the thyroid gland (cancer).

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Royal Society (2001) The Health hazards of depleted uranium munitions. Part I London: The Royal Society

Royal Society (2002) The Health hazards of depleted uranium munitions. Part II London: The Royal Society

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Schroeder H, Heimers A, Frentzel Beyme R, Schott A and Hoffmann W (2003) 'Chromosome aberration analysis in peripheral lymphocytes of Gulf War and Balkans War veterans'. Rad. Prot. Dosim 103 (3) 211-219

Sheppard, P.R., R.J. Speakman, G. Ridenour, and M.L. Witten. 2007. Temporal variability of tungsten and cobalt in Fallon, Nevada. Environmental Health Perspectives 115:715-719. Speirs FW (1949) The influence of energy absorption and electron range on dosage in irradiated bone. Brit. J. Radiol. 22 521-533

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Sztajnkrycer, M. D. and E. J. Otten. "Chemical and radiological toxicity of depleted uranium." Mil.Med. 169.3 (2004): 212-16.

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Wise SS, Thompson WD, El-Makarim Abouseissa A, Mason MD and Wise JP (2007) Particulate Depleted Uranium is cytotoxic and clastogenic to human lung cells Chem.Res.Toxicol. ASAP article 10.1021/tx700026r S0893-228x(70)00026-7

A, Zaire R, Notter M and Thiel E (1997) Unexpected rates of chromosome instabilities and alteration of hormone levels in Namibian Uranium Miners. Radiation

Research 147 (5) 579-584

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Tables Table 1. Photon mass attenuation coefficients and attenuation coefficients (absorption coefficients) for different selected photon energies compared for Uranium and skeletal tissue (ICRU44). [Hubbell JH and Seltzer SM Ionizing Radiation Division, NIST Gaithersburg MD 20899 1989]
m

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m

Energy (keV) 2 4 10 20 50 100 200

Uranium
m

muscle 500 70 5 0.8 (0.6) 0.2(0.05) 0.15 (0.03) 0.13 (0.03)

Uranium 36100 24700 3800 1330 (1235) 190 (171) 24.7 (15.2) 24.7 (15.2)

muscle 500 70 5 0.8 (0.6) 0.2 (0.05) 0.15 (0.03) 0.13 (0.03)

1900 1300 200 70 (65) 10 (9) 1.3 (0.8) 1.3 (0.8)

Ratio : U/muscle 72.2 352 760 1662 (2058) 950 (3420) 164 (506) 190 (506)

Table 2. Approximate range in microns for Uranium,Uranium Oxide and living tissue for electrons of different energies. (Based on values in Krane 1988)

Electron energy and example Uranium (Q = 19) 500keV (Sr-90 V-particle) 26 200keV photoelectron 13 100keV photoelectron 5 50keV photoelectron 2.1 10 keV photoelectron/ 0.4 Auger electron

Energies below 20keV may have much shorter ranges and ionisation per micron than CSDA approximation shown here suggests (see text).

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Uranium Oxide (Q = 10) 50 25 9 4 0.8

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Tissue (Q = 1) 500 250 90 40 8

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Table 3 Penetration distance (microns) of 75% of photons of different energies in Uranium, Uranium Oxide and living tissue. (Half penetration depth = 0.693/; (Wrane 1988)). Photon energy Uranium Uranium Oxide (Q = 19) cms (Q = 10) cms *200keV 670 1300 *100keV 670 1300 50keV 60 120 20keV 0.0008 (8) 0.0015 (15) 10 keV 0.0003 (3) 0.0005 (5) Tissue (Q = 1) cms 3460000 3460000 210000 1.7 0.2

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Fig 1 Natural background gamma radiation spectrum obtained using a 2" NaI (Tl) detector near Bristol in 2002. 1000second count period. (Green Audit)

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