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PubMed1975

[Functional study of metal and radiation in the mechanism of toxic action of plutonium injected in its elemental form].

A ponderal variations study of rats contaminated either with the same metal mass of two isotopes 238Pu and 239Pu or with an equal activity level entitles us to conclude that plutonium toxicity for below 50 muCi/kg levels arises from particles alpha. For higher levels, about 120 muCi/kg, the quantity effect of metal has an influence on localisation and repartition of toxicity. Beneficial effect of oxygenotherapy for 120 muCi/kg appears only after a delay of several days, the time required for toxic manifestation, confirming in acute intoxication, the function of ionising radiation emitted by the metal.

Alpha Particles↗

PubMed2003

Sizing alpha emitting particles of aged plutonium on personal air sampler filters using CR-39 autoradiography.

Methods have been developed to assess the size distribution of alpha emitting particles of reactor fuel of known composition captured on air sampler filters. The sizes of uranium oxide and plutonium oxide particles were determined using a system based on CR-39 solid-state nuclear track detectors. The CR-39 plastic was exposed to the deposited particles across a 400 microm airgap. The exposed CR-39 was chemically etched to reveal clusters of tracks radially dispersed from central points. The number and location of the tracks were determined using an optical microscope with an XY motorised table and image analysis software. The sample mounting arrangement allowed individual particles to be simultaneously viewed with their respective track cluster. The predicted diameters correlated with the actual particle diameters, as measured using the optical microscope. The efficacy of the technique was demonstrated with particles of natural uranium oxide (natUO2) of known size, ranging from 4 to 150 microm in diameter. Two personal air sampler (PAS) filters contaminated with actinide particles were placed against CR-39 and estimated to have size distributions of 0.8 and 1.0 microm activity median aerodynamic diameter (AMAD).

Aerosols↗

PubMed2004

Lethal sectoring, genomic instability, and delayed division delay in HeLa S3 cells surviving alpha- or X-irradiation.

Lethal sectoring (LS) is the process for survival in which lethal damage remaining in irradiated cells is eliminated as lethal sector (offspring without reproductive integrity). This process occurs through the postirradiation 1st to 4th divisions with the accompanying appearance of a clonogenic progenitor (clonogen) (clonogenic sectoring: CS). The features of LS or CS and genomic instability (GI) were explored by analyzing the pedigrees of HeLa cells surviving alpha- (0.45 Gy) or X-irradiation (3 Gy) (20% survival dose). Most (approximately 70%) of the lethal latent damage was eliminated from alpha-particle survivors through the 1st to 2nd divisions, but it persisted in X-ray survivors until the 2nd generation. Although the frequency of CS was similar to that of LS for alpha-irradiation, CS was higher than LS for X-irradiation. Nonlethal damage remaining in the clonogens led to an elevated incidence of delayed cell death in their progeny. The mean incidence was higher for alpha-particle (16.3%) than X-ray survivors (8.3%), indicating the greater potentiality for GI by alpha-particles. Evidence is available to suggest the intrinsic difference in the mechanisms of GI induction by these two radiations: the association of misrepaired clustered DNA damage (CD) with alpha-particles and unrepaired PLD with X-rays. A novel phenomenon, "delayed division delay (DDD)" was noticed, though occasionally (approximately 10% per cell), with the progeny during the postirradiation 1st-3rd generations. DDD was much longer in alpha- (mean: approximately 11 h) than X-irradiated cells (approximately 4 h). Supposedly DDD was triggered by delayed chromosome breakage. However, a significant shortening of cell-cycle time at the postirradiation 1st generation was recognized with X-ray survivors.

Alpha Particles↗

PubMed2001

Theoretical estimation of absorbed dose to organs in radioimmunotherapy using radionuclides with multiple unstable daughters.

The toxicity and clinical utility of long-lived alpha emitters such as Ac-225 and Ra-223 will depend upon the fate of alpha-particle emitting unstable intermediates generated after decay of the conjugated parent. For example, decay of Ac-225 to a stable element yields four alpha particles and seven radionuclides. Each of these progeny has its own free-state biodistribution and characteristic half-life. Therefore, their inclusion for a more accurate prediction of absorbed dose and potential toxicity requires a formalism that takes these factors into consideration as well. To facilitate the incorporation of such intermediates into the dose calculation, a previously developed methodology (model 1) has been extended. Two new models (models 2 and 3) for allocation of daughter products are introduced and are compared with the previously developed model. Model 1 restricts the transport to a function that yields either the place of origin or the place(s) of biodistribution depending on the half-life of the parent radionuclide. Model 2 includes the transient time within the bloodstream and model 3 incorporates additional binding at or within the tumor. This means that model 2 also allows for radionuclide decay and further daughter production while moving from one location to the next and that model 3 relaxes the constraint that the residence time within the tumor is solely based on the half-life of the parent. The models are used to estimate normal organ absorbed doses for the following parent radionuclides: Ac-225, Pb-212, At-211, Ra-223, and Bi-213. Model simulations are for a 0.1 g rapidly accessible tumor and a 10 g solid tumor. Additionally, the effects of varying radiolabled carrier molecule purity and amount of carrier molecules, as well as tumor cell antigen saturation are examined. The results indicate that there is a distinct advantage in using parent radionuclides such as Ac-225 or Ra-223, each having a half-life of more than 10 days and yielding four alpha particles per parent decay, in that lower doses to normal organs result for a given tumor dose in comparison to those radionuclides yielding fewer alpha particles. In model 2, which accounts for transit time through the blood, a dose of 20 Gy to a rapidly accessible 0.1 g tumor will result in a liver and kidney dose of 1.7 and 0.9 Gy, respectively from Ac-225. An equivalent dose to tumor from Ra-223 would yield a maximum normal organ dose of 0.4 and 0.3 Gy to bone and small intestines, respectively; the corresponding absorbed dose to small intestines from Pb-212 and Bi-213 is 2.2 and 3.0 Gy, respectively.

Alpha Particles↗

PubMed1999

Mutation induction by different types of radiation at the Hprt locus.

Mutation induction at the Hprt locus in Chinese hamster cells was studied after exposure to ultraviolet light, X-rays and alpha particles. While mutant frequency as a function of dose or fluence followed a linear-quadratic relationship with UV and X-rays, it showed a linear dependence for alpha particles. If mutant frequency is plotted vs. the logarithm of surviving fraction, a linear relationship is found in all cases although with different slopes. These are about equal with the two types of ionising radiations but about 10 times larger for UV. They can be used as a measure of mutagenic potential and are termed mutagenicity. It is shown that this parameter is correlated with the maximum of mutant yield, i.e., the number of mutants per cell at risk. It is concluded from this analysis that the maximum mutant yield is always found at doses or fluences which lead to 37% survival irrespective of the kind of radiation. If mutation induction is measured in X-irradiated cells after pre-exposure to UV, mutant frequency is higher than expected on the basis of independent action of the two radiations. Deletion spectra were determined by using multiplex polymerase chain reaction. It was found that the background of spontaneous mutants varied considerably and showed frequently repetitive patterns, presumably because of clonal expansion of pre-formed mutants. UV-induced mutants did not contain any deletions, while those with both X-rays and alpha particles the majority displayed partial and total deletions. Based on a total number of 134 X-ray- and 192 alpha-induced mutants, it is concluded that the total fraction of mutant clones without deletions (partial or total) is about 40% for X-rays and only about 20% for alpha-particles.

Alpha Particles↗

PubMed2003

Quantitative comparisons of cancer induction in humans by internally deposited radionuclides and external radiation.

PURPOSE: To compare quantitative estimates of lifetime cancer risk in humans for exposures to internally deposited radionuclides and external radiation. To assess the possibility that risks from radionuclide exposures may be underestimated. MATERIALS AND METHODS: Risk estimates following internal exposures can be made for a small number of alpha-particle-emitting nuclides. (1) Lung cancer in underground miners exposed by inhalation to radon-222 gas and its short-lived progeny. Studies of residential (222)Rn exposure are generally consistent with predictions from the miner studies. (2) Liver cancer and leukaemia in patients given intravascular injections of Thorotrast, a thorium-232 oxide preparation that concentrates in liver, spleen and bone marrow. (3) Bone cancer in patients given injections of radium-224, and in workers exposed occupationally to (226)Ra and (228)Ra, mainly by ingestion. (4) Lung cancer in Mayak workers exposed to plutonium-239, mainly by inhalation. Liver and bone cancers were also seen, but the dosimetry is not yet sufficiently good enough to provide quantitative estimates of risks. Comparisons can be made between risk estimates for radiation-induced cancer derived for radionuclide exposure and those derived for the A-bomb survivors, exposed mainly to low-LET (linear energy transfer) external radiation. Data from animal studies, using dogs and rodents, allow comparisons of cancer induction by a range of alpha- and beta-/gamma-emitting radionuclides. They provide information on relative biological effectiveness (RBE), dose-response relationships, dose-rate effects and the location of target cells for different malignancies. RESULTS: For lung and liver cancer, the estimated values of risk per Sv for internal exposure, assuming an RBE for alpha-particles of 20, are reasonably consistent with estimates for external exposure to low-LET radiation. This also applies to bone cancer when risk is calculated on the basis of average bone dose, but consideration of dose to target cells on bone surfaces suggests a low RBE for alpha-particles. Similarly, for leukaemia, the comparison of risks from alpha-irradiation ((232)Th and progeny) and external radiation suggest a low alpha RBE; this conclusion is supported by animal data. Risk estimates for internal exposure are dependent on the assumptions made in calculating dose. Account is taken of the distribution of radionuclides within tissues and the distribution of target cells for cancer induction. For the lungs and liver, the available human and animal data provide support for current assumptions. However, for bone cancer and leukaemia, it may be that changes are required. Bone cancer risk may be best assessed by calculating dose to a 50 micro m layer of marrow adjacent to endosteal (inner) bone surfaces rather than to a single 10 micro m cell layer as currently assumed. Target cells for leukaemia may be concentrated towards the centre of marrow cavities so that the risk of leukaemia from bone-seeking radionuclides, particularly alpha emitters, may be overestimated by the current assumption of uniform distribution of target cells throughout red bone marrow. CONCLUSIONS: The lifetime risk estimates considered here for exposure to internally deposited radionuclides and to external radiation are subject to uncertainties, arising from the dosimetric assumptions made, from the quality of cancer incidence and mortality data and from aspects of risk modelling; including variations in baseline rates between populations for some cancer types. Bearing in mind such uncertainties, comparisons of risk estimates for internal emitters and external radiation show good agreement for lung and liver cancers. For leukaemia, the available data suggest that the assumption of an alpha-particle RBE of 20 can result in overestimates of risk. For bone cancer, it also appears that current assumptions will overestimate risks from alpha-particle-emitting nuclides, particularly at low doses.

Animals↗

PubMed2001

Oncoprotein expression in human breast epithelial cells transformed by high-LET radiation.

PURPOSE: The aim of the present work was to analyze the expression of oncoproteins that are frequently altered in breast cancer with specific phenotypic stages in the neoplastic process. MATERIALS AND METHODS: Expression of c-myc, c-jun, c-Ha-ras and the tumor suppressor gene p53 oncoproteins were examined by immunohistochemical staining coupled with confocal microscopy in transformed and tumorigenic human breast epithelial cells induced by high-LET alpha-particles (150 kcV/microm). RESULTS: MCF-10F cells, irradiated with single and double doses of 60 cGy alpha-particles and subsequently treated with cstrogen, showed gradual phenotypic changes including altered morphology, increased cell proliferation relative to control, anchorage-independent growth, invasive capabilities and tumorigenicity in nude mice. MCF-10F cells irradiated with a second dose of 60 cGy alpha-particles after estrogen treatment (60 cGy+ E/60 cGy+E) showed tumorigenicity both in SCII) and nude mice. Alterations in the protein expression of several oncogenes including c-myc, c-jun, c-Ha-ras and the tumor suppressor gene p53 were detected in alpha-particle-irradiated cells and in those cells subsequently cultured in the presence of estrogen. The expression level of these oncoproteins correlated with the progressive nature of the neoplastic process. CONCLUSION: These studies suggest that overexpression of several oncoproteins is important in the neoplastic transformation of human breast epithelial cells induced by high-LET radiation. In addition, use of endocrine factors such as estrogen allows the examination of various aspects of protein expression providing the basis for understanding the complex interactions of hormones and genes.

Animals↗

PubMed2006

Absorbed dose in target cell nuclei and dose conversion coefficient of radon progeny in the human lung.

To calculate the absorbed dose in the human lung due to inhaled radon progeny, ICRP focussed on the layers containing the target cells, i.e., the basal and secretory cells. Such an approach did not consider details of the sensitive cells in the layers. The present work uses the microdosimetric approach and determines the absorbed alpha-particle energy in non-spherical nuclei of target cells (basal and secretory cells). The absorbed energy for alpha particles emitted by radon progeny in the human respiratory tract was calculated in basal- and secretory-cell nuclei, assuming conical and ellipsoidal forms for these cells. Distributions of specific energy for different combinations of alpha-particle sources, energies and targets are calculated and shown. The dose conversion coefficient for radon progeny is reduced for about 2mSv/WLM when conical and ellipsoidal cell nuclei are considered instead of the layers. While changes in the geometry of secretory-cell nuclei do not have significant effects on their absorbed dose, changes from spherical to conical basal-cell nuclei have significantly reduced their absorbed dose from approximately 4 to approximately 3mGy/WLM. This is expected because basal cells are situated close to the end of the range of 6MeV alpha particles. This also underlines the significance of better and more precise information on targets in the T-B tree. A further change in the dose conversion coefficient can be achieved if a different weighting scheme is adopted for the doses for the cells. The results demonstrate the necessity for better information on the target cells for more accurate dosimetry for radon progeny.

Humans↗

PubMedDate not supplied

Tumorigenicity, oncogene transfection, and radiosensitivity.

PURPOSE: Reports that the incorporation of exogenous oncogenes confer radioresistance have excited interest and controversy. We investigate whether human cell lines transformed to a malignant phenotype by gamma-rays or by chemicals became radioresistant. MATERIALS AND METHODS: Rodent intestinal epithelial cells immortalized by the HPV virus, human immortalized bronchoepithelial cells and their malignant counterparts transformed by alpha-particles, uroepithelial cells and their malignant counterparts transformed either by alpha-particles or methylcholanthrine-4, and osteosarcoma cells and their nonmalignant counterparts into which the Rb gene had been introduced were used. Dose response curves for all of these cell lines were obtained by exposure to cesium 137 gamma-rays at a dose-rate of 1.18 Gy/min. RESULTS: There was a dramatic increase in resistance to gamma-rays when H-ras was transfected into rodent intestinal epithelial cells. By contrast, in the case of the three human cell lines used, no consistent or significant change of radiosensitivity occurred when normal cells were transformed to a malignant state by alpha-particles or by a chemical carcinogen. CONCLUSIONS: Experiments involving the introduction of foreign oncogenes to cause tumorigenicity and accompanying radioresistance do not have direct relevance in human tumors. In a number of different instances, the conversion to malignancy by means that more closely reflect what happens in practice (i.e., by radiation or a chemical carcinogen) is not necessarily accompanied by an increased radioresistance to low doses of radiation.

Alpha Particles↗

PubMed1980

The induction of chromosome aberrations in human lymphocytes by alpha-radiation.

Human blood has been irradiated with alpha-particles from an external source of curium-242. The collimated alpha-particles entered the blood with an energy of 4-9 MeV and were almost completely absorbed by the blood. After culturing for 48 hours, the dicentric yield in the lymphocytes at the first metaphase was measured as a function of dose to the blood. The yield was linear with dose up to 400 rad with a slope of 28x6 X 10(4) dicentrics/cell per rad. This is equivalent to an initial slope r.b.e. of 17x9 with respect to cobalt-60 gamma-rays. This value disagrees with the only two other published values in the literature. Reasons for this disagreement are discussed. Compared with neutron r.b.e values obtained in this laboratory the alpha-particle values we observe are surprisingly low. A model is proposed which predicts low values of r.b.e. for chromosome aberration production using radiations of high LET. The low values occur because there is a distribution of specific energy between cells which causes a selective removal of cells likely to contain higher numbers of aberrations.

Alpha Particles↗

PubMed2006

Current status and perspectives in alpha radioimmunotherapy.

Systemic administration of radiolabeled antibody directed against tumor antigens in radioimmunotherapy (RIT) enables to specifically target the cancer cells and to destroy them. So far, this strategy has proven its efficiency in the treatment of some hematological cancers with antibodies labeled with beta emitting radionuclides. In the last 2 decades, availability of short half life alpha emitters prompted to consider their use in RIT. Contrary to beta particles, alpha particles have a short path length and display a high lineic energy transfer. Those physical characteristics open new fields of clinical applications complementary to beta-RIT. To date, alpha-RIT is still at a preclinical stage of development: the radiolabeling methods need to be optimized to ensure in vivo stability of the radiopharmaceuticals. Some radionuclides have complex decay schemes with daughters emitting further alpha particles whose toxicity needs to be investigated. The modalities of administration of radiolabeled antibodies in animal models require also to be improved for delivering higher doses to tumor targets. A comprehensive analysis of the specific events occurring at cell or tissue level in response to alpha irradiation would be of great interest in order to define the best therapeutic association for residual disease or consolidation treatments. This approach has been proven to be efficient in increasing antitumor response either by using high doses with organ protection (kidney, bone marrow) or by a synergistic effect between alpha-RIT and associated treatments, such as chemotherapy.

Alpha Particles↗

PubMed2006

Constitutive nitric oxide acting as a possible intercellular signaling molecule in the initiation of radiation-induced DNA double strand breaks in non-irradiated bystander cells.

The initiation and propagation of the early processes of bystander signaling induced by low-dose alpha-particle irradiation are very important for understanding the underlying mechanism of the bystander process. Our previous investigation showed that the medium collected from cell culture exposed to low-dose alpha-particle rapidly induced phosphorylated form of H2AX protein foci formation among the non-irradiated medium receptor cells in a time-dependent manner. Using N(G)-methyl-L-arginine, 4-amino-5-methylamino-2',7'-difluorofluorescein diacetate and N(omega)-nitro-L-arginine (L-NNA) treatment before exposure to 1 cGy alpha-particle, we showed in the present study that nitric oxide (NO(*)) produced in the irradiated cells was important and necessary for the DNA double strand break inducing activity (DIA) of conditioned medium and the generation of NO(*) in irradiated confluent AG1522 cells is in a time-dependent manner and that almost all NO(*) was generated within 15 min post-irradiation. Concurrently, the kinetics of NO(*) production in the medium of irradiated cells after irradiation was rapid and in a time-dependent manner as well, with a maximum yield observed at 10 min after irradiation with electron spin resonance analysis. Furthermore, our results that 7-Nitroindazole and L-NNA, but not aminoguanidine hemisulfate, treatment before exposure to 1 cGy alpha-particle significantly decrease the DIA of the conditioned medium suggested that constitutive NO(*) from the irradiated cells possibly acted as an intercellular signaling molecule to initiate and activate the early process (<or=30 min) of bystander response after low-dose irradiation.

Alpha Particles↗

PubMed1996

Targeted therapy using alpha emitters.

Radionuclides such as 211At and 212Bi which decay by the emission of alpha-particles are attractive for certain applications of targeted radiotherapy. The tissue penetration of 212Bi and 211At alpha-particles is equivalent to only a few cell diameters, offering the possibility of combining cell-specific targeting with radiation of similar range. Unlike the beta-particles emitted by radionuclides such as 131I and 90Y, alpha-particles are radiation of high linear energy transfer and thus greater biological effectiveness. Several approaches have been explored for targeted radiotherapy with 212Bi- and 211At-labelled substances including colloids, monoclonal antibodies, metabolic precursors, receptor-avid ligands and other lower molecular weight molecules. An additional agent which exemplifies the promise of alpha-emitting radiopharmaceuticals is meta-[211At]astatobenzylguanidine. The toxicity of this compound under single-cell conditions, determined both by [3H]thymidine incorporation and by limiting dilution clonogenic assays, for human neuroblastoma cells is of the order of 1000 times higher than that of meta-[131I] iodobenzylguanidine. For meta-[211At] astatobenzylguanidine, the Do value was equivalent to only 6-7 211At atoms bound per cell. These results suggest that meta-[211At] astatobenzylguanidine might be valuable for the targeted radiotherapy of micrometastatic neuroblastomas.

Alpha Particles↗

PubMed1987

Influence of the physical state and straggling on the computation of the radiation dose due to radon daughters deposited in the lung.

The effect of the physical state (phase) of the absorbing medium and the energy straggling of the alpha particles on the calculation of the radiation dose due to the daughter products of radon deposited in the lung have been studied in detail. The stopping power data for alpha particles in water and water vapour have been used. It has been found that the effect of straggling on the stopping power calculations is small, and therefore its contribution to dose calculations is negligible. The phase effect has been found to be dependent on the energy of the alpha particles and the depth in the medium. If the stopping power of water vapour is used instead of that for liquid water, the dose may be overestimated by 5-20 and 1-11% for 6 and 7.7 MeV alpha particles, respectively, at the beginning of alpha range, and underestimated by 15 and 40% respectively for the above energies at the end of the range.

Dose-Response Relationship, Radiation↗

PubMed2000

Lung cancer mortality among male nuclear workers of the Mayak facilities in the former Soviet Union.

An analysis of lung cancer mortality in a cohort of 1,669 Mayak workers who started their employment in the plutonium and reprocessing plants between 1948 and 1958 has been carried out in terms of a relative risk model. Particular emphasis has been given to a discrimination of the effects of external gamma-ray exposure and internal alpha-particle exposure due to incorporated plutonium. This study has also used the information from a cohort of 2,172 Mayak reactor workers who were exposed only to external gamma rays. The baseline lung cancer mortality rate has not been taken from national statistics but has been derived from the cohort itself. For both alpha particles and gamma rays, the results of the analysis are consistent with linear dose dependences. The estimated excess relative risk per unit organ dose equivalent in the lung due to the plutonium alpha particles at age 60 equals, according to the present study, 0.6/Sv, with a radiation weighting factor of 20 for alpha particles. The 95% confidence range is 0.39/Sv to 1.0/Sv. For the gamma-ray component, the present analysis suggests an excess relative risk for lung cancer mortality at age 60 of 0.20/Sv, with, however, a large 95% confidence range of-0.04/Sv to 0.69/Sv.

Alpha Particles↗

PubMed1997

Structure of glycogen particles in organ of Corti's outer hair cells in three rodent species.

Organ of Corti's outer hair cells are one of the few cell types in mammals to contain large cytoplasmic glycogen stores, and the only one in the adult auditory receptor. Previous reports on the structure and distribution of glycogen in the adult organ of Corti were mainly based on light microscopy histo- and cytochemical methods, and the scare EM studies on the topic relied on techniques which were not sensitive or specific enough. Furthermore, it has been reported that glycogen particles are not present in outer hair cells of all species. A first goal of the present study was to describe the ultrastructure of glycogen stores in organ of Corti's outer hair cells in Guinea pig, rat, and mouse, using the periodic acid-thiocarbohydrazide-silver proteinate method. In addition, differences in the subcellular and cochleotopic distribution of this substance were analyzed. In the adult organ of Corti only the outer hair cells contain glycogen stores. Present throughout their cytoplasm, these deposits appear either as single beta particles, or as aggregates of these, forming alpha particles. Though most alpha particles are round, some appear long and conspicuously straight in longitudinal sections of those cells near the apex of the cochlea, and they seem to be apposed to some filamentous structure. On the other hand, when the cells are sectioned transversely the larger aggregates of glycogen particles follow a curved course. Since outer hair cells of the apical region of the cochlea contain a bundle of contractile microfilaments, our results suggest that glycogen is associated with the contractile apparatus of these cells. This hypothesis is in good accordance with previous experimental data which suggest that glycogen is used as energy source for the contractile movements of outer hair cells.

Aging↗

PubMed1994

Primary liver tumors among Danish patients exposed to Thorotrast.

The potential carcinogenic effects of internally deposited alpha-particle-emitting nuclides, notably plutonium, in the liver in humans are unknown but are of concern in relation to exposures from the nuclear industry. However, patients injected with the radiographic contrast medium Thorotrast are chronically exposed to alpha-particle radiation from 232ThO2 in the liver. Among 1003 patients injected with Thorotrast, 584 of whom were alive 15 years after the injection and 40 at the end of follow-up, a total of 127 liver cancers were diagnosed, 45 of which were hepatocellular carcinomas, 41 cholangiocarcinomas and 33 hemangiosarcomas. The median time from injection to diagnosis was 35 years (range 18-48) and the cumulative frequency was 55.4% after 48 years. In univariate and multivariate analyses, the cumulative frequency of liver cancer was best described as a function of the estimated mean cumulative alpha-particle radiation dose to the liver 15 years ago, being independent of age, gender and volume of injected Thorotrast. This may be interpreted to mean that the liver cancer rate is not related to the dose rate and that the period from malignant transformation to diagnosis of cancer is 15 years. The risk of liver carcinogenesis induced by alpha-particle radiation, assuming 15 years from induction to diagnosis, was estimated to be 712 cases/10(4) persons per gray. This value is considerably higher than estimated earlier.

Adolescent↗

PubMed1993

Induction and rejoining of DNA double-strand breaks in V79-4 mammalian cells following gamma- and alpha-irradiation.

The induction and rejoining of DNA double-strand breaks (dsbs) in V79-4 mammalian cells following irradiation by 60Co gamma-rays and 238Pu alpha-particles (average LET 120 keV microns-1) under aerobic conditions have been determined using both the sucrose sedimentation and filter elution techniques under non-denaturing conditions. Cellular inactivation was also determined. The dependence of the initial yield of dsbs at 277 K on dose under aerobic conditions is linear with a relative biological effectiveness (RBE) for alpha-particles of 0.85 +/- 0.14 (sedimentation) and 0.68 +/- 0.12 (elution) compared with 60Co gamma-rays. The ability of the cells to rejoin dsbs at 310K is significantly reduced for alpha-irradiations with only 30-50% rejoined for a 3-h incubation period. With low LET radiation, > 90% of the dsbs are rejoined within 3 h at a dose of 20 Gy. The RBE for cellular inactivation was determined to be 4.0 at the 1% survival level. From the cellular dimensions and the D0-value for cellular inactivation by alpha-particles, it is determined that, on average, 4.7 tracks traverse the cell nucleus per lethal lesion. Under hypoxic conditions, the RBE values for induction of dsbs and cellular inactivation (10% level) by alpha-particles are approximately 3.0 and approximately 11.8 respectively. From these findings, it is suggested that the residual DNA damage and not the initial damage is reflected in the cellular inactivation. It is inferred that the difference in repair of the various lesions is a reflection of the differences in the complexity of the clustered damage produced by these radiations.

Alpha Particles↗