Higher Relative Biological Effectiveness Research Articles

Killing of Feline T-Lymphocytes by Gamma-Rays and Energetic Carbon Ions

High linear energy transfer (LET) heavy charged particles have previously been applied clinically to human cancer radiotherapy because of their excellent physical properties of selective dose distribution and higher relative biological effectiveness (RBE) for human; however, such an approach has yet to be applied to cat patients. The present study investigates the biological effectiveness of low-LET gamma-rays (0.2 keV/micro m) compared to high-LET carbon ions (114 keV/micro m) in feline T- lymphocyte FeT-J cells. Clonogenic survival analysis revealed that the RBE value of carbon ions was 2.98 relative to a 10% survival dose (D(10)) by gamma-rays, and that the inactivation cross-section in cells exposed to gamma-rays and carbon ions was 0.023 and 38.9 micro m(2), respectively. Terminal deoxynucleotidyl transferase (TdT)-mediated dUTP-biotin nick end labeling (TUNEL) analysis revealed that TUNEL-positive frequency in carbon-irradiation cells is higher than for gamma-irradiated cells against exposure to the same physical doses, but that very little difference in TUNEL-positive frequency is observed between cells exposed to the respective D(10) dose of gamma-rays. Our data thus indicate that carbon ions are more effective for cell killing than gamma-rays at the same physical doses, but kill cells to an extent that is comparable to gamma-rays at the same biological doses. Carbon ion radiotherapy is therefore a promising modality for cat patients.

Therapeutic purpose 9C beams produced in the secondary beam line at HIMAC

Due to the favorable characteristics of heavy-ion beams such as dose localization as well as high relative biological effectiveness, heavy-ion cancer therapy is attracting growing interests all over the world. The application of β-delayed particle decay beams like 9C ions in cancer therapy is expected to further improve the treatment efficacy of the modality of heavy-ions. For the first time 9C beams were produced in the secondary beam line (SBL) of the HIMAC facility with a primary 12C beam of 430 MeV/n. The production conditions providing a 9C beam with higher production rate and purity were optimized using different thick production targets and degraders. The results show setting the momentum acceptance to the full value of 5% the production rate is 9.07 × 10 −6 and the purity is 82.88% for the produced 9C beam under the optimal condition. Because of the large momentum spread for a secondary beam, the momentum distribution of the produced 9C beam at the optimal condition was measured. The momentum among the beam had a nearly Gaussian profile with a standard deviation of 26.1 MeV/c/n and the largest component of the momenta appeared around 838.9 MeV/c/n. In order to form a relatively large uniform irradiation field being appropriate to further biological experiments for the produced 9C beam, the scanning magnets in the irradiation system of the SBL, operating in a wobbling mode, was used. A uniform irradiation field of 20 mm in diameter could be achieved with homogeneity of 93.8%. The work presented in this paper provides a substantial basis for the further studies with 9C beams for the therapeutic purpose.

Comparative Microdosimetry of Photoelectrons and Compton Electrons: An Analysis in Terms of Generalized Proximity Functions

A current discussion on mammography screening is focused on claims of high relative biological effectiveness (RBE) of mammography X rays compared to conventional 200 kV X rays. An earlier assessment in terms of the electron spectra of these radiations has led to the conclusion that the RBE is bound to be less than 2, regardless of specific model assumptions and the microdosimetric properties of electrons. The present study extends this result in terms of the microdosimetric proximity function, t(x), for electrons, which is essentially the spatial auto-correlation function of energy within particle tracks. If pairs of DNA lesions, e.g. chromosome breaks or deletions, bring about the observed damage, the value t(x) determines for a specified radiation the relative frequency of pairs of lesions a distance x apart. The effectiveness of the radiation is thus proportional to an average of the values of t(x) over the distances, x, for which lesions can combine. The analysis suggests that 15 keV electrons can have a low-dose relative biological effectiveness (RBE(M)) of 1.6 relative to 40 keV electrons if the interaction distances do not exceed about 1 micro m. An extension of the concept, the reduced proximity function, t(delta)(x), permits the inclusion of models with an energy threshold, such as delta = 100 eV, 500 eV or 2 keV, for the formation of each of the DNA lesions. This makes it possible to assess the potential impact of the Auger electrons which accompany most photoelectrons, but only a minority of the Compton electrons. It is found that the Auger electrons could make photoelectrons substantially more effective than Compton electrons at energies below 10 keV but not at energies above 15 keV. The conclusions obtained for the RBE of 15 keV electrons relative to 40 keV electrons will be roughly representative of the RBE of mammography X rays relative to conventional 200 kV X rays.

Reduction of survival and induction of chromosome aberrations in tobacco irradiated by carbon ions with different linear energy transfers

Purpose : To determine the relationship between linear energy transfer (LET) and the relative biological effectiveness (RBE) for survival reduction and chromosome aberration induction in plants. Materials and methods : Tobacco seeds were exposed to carbon ions having LET ranging from 92 to 260 keV μ m -1. Survival rate was determined at 7 weeks after sowing. Chromosome aberrations were observed when the root length reached about 0.5mm (immediately after radicle emergence), 3 and 10 mm. Results : The RBE for both endpoints increased with increasing LET and showed the highest value at 230 keV μ m -1. The highest RBE was 65.0 for survival reduction and 52.5 for chromosome aberration induction. The types and yield ratio of chromosome aberrations such as fragments and bridges were not affected by radiation type at 0.5mm root length. As the roots elongated from 0.5 to 10 mm, the frequency of aberrant cells gradually decreased. The number of cells with fragments decreased faster than the number of cells with bridges. The decrement of chromosome aberrations appeared to be slower in roots irradiated by carbon ions than in roots irradiated by γ -rays. Conclusions : The results show a close relationship between survival reduction and chromosome aberration induction in plants. The types and yield ratio of initial chromosome aberrations did not differ among γ -rays and carbon ions with different LET.

Boron neutron capture therapy for malignant gliomas

Boron neutron capture therapy (BNCT) represents a promising modality for a relatively selective radiation dose delivery to the tumour tissue. Boron-10 nuclei capture slow ‘thermal’ neutrons preferentially and, upon capture, promptly undergo 10B(n,α)7Li reaction. The ionization tracks of energetic and heavy lithium and helium ions resulting from this reaction are only about one cell diameter in length (∼ 14 μm). Because of their high linear energy transfer (LET) these ions have a high relative biological effectiveness (RBE) for controlling tumour growth. The key to effective BNCT of tumours, such as glioblastoma multiforme (GBM), is the preferential accumulation of boron-10 in the tumour, including the infiltrating GBM cells, as compared with that in the vital structures of the normal brain. Provided that a sufficiently high tumour boron-10 concentration (∼109 boron-10 atoms/cell) and an adequate thermal neutron fluence (∼ 1012 neutrons/ cm2) are achieved, it is the ratio of the boron-10 concentration in tumour cells to that in the normal brain cells that will largely determine the therapeutic gain of BNCT.

Micronuclei and cell survival in human liver cancer cells irradiated by 25MeV/u (40)Ar14(+).

Heavy ions with high linear energy transfer (LET) have the following advantages as compared with the conventional X-rays and γ-rays therapy: a better physical selectivity, a higher relative biological effectiveness (RBE), a greater therapeutic gain factor (TGF), a smaller oxygen enhancement ratio (OER) for LET > 200 keV/μm, positrons emitted from nuclear reaction products offering the condition of monitoring heavy ion position in tissue, and so on. During the mid 1970s, 450 patients were treated with heavy ions, mostly neon, at the Bevalac of Lawrence Berkeley Laboratory (LBL), United States[1]. Promising results with neon ions were reported when compared with the conventional radiotherapy for soft tissue sarcoma, bone sarcoma and prostate cancer[2,3]. In 1994, the Heavy Ion Medical Accelerator in Chiba (HIMAC) of Japan was designed to deliver beams of ions, helium to argon, to energies in the range of 100 MeV/u-800 MeV/u. Carbon ions were used for clinical treatment. By August 1997, a total of 301 patients had been treated with carbon ions[4]. The treatment was started at GSI, Darmstadt, Germany in December 1997. Two patients suffering from tumors at the base of skull were treated with five and four fractions of carbon ions respectively[5]. In 1995, HIRFL (Heavy Ion Research Facility in Lanzhou, China) began the basic researches of cancer therapy with heavy ions such as carbon, oxygen and argon. In order to collect basic data for clinical therapy, we studied and discussed the dynamic changes of micronuclei and cell survival in human liver cancer cells SMMC-7721 irradiated by 25 MeV/u40-Ar 14+.

The general relation between tissue response to x-radiation (α/β-values) and the relative biological effectiveness (RBE) of protons: Prediction by the Katz track-structure model

Purpose : Experimental data suggest that the relative biological effectiveness (RBE) of protons compared to x-rays may be determined by the α / β -ratio of the x-ray survival curve. The data are referring to the centre of a spread-out Bragg peak (SOBP) formed to deliver a homogeneous dose to the tumour by modulating the proton energy. In an effort to explore the basis for this observation, calculations were performed to investigate the response of different biological targets through a range of proton energies and doses. Materials and methods : To describe the x-ray survival curve, the parameters of the linear-quadratic equation, α and β, as well as those of the multi-target/single-hit equation, n and D 0, were considered. These parameters were varied to investigate the RBE using the Katz track-structure model. Known cell line characterizations, as well as different hypothetical cells assuming different α / β -ratios but similar target size parameters in the framework of the track-structure theory, were considered. Results : The RBE was found to increase with increasing α / β when the parameter n was varied, but to decrease with increasing α / β when D 0 was varied. This held when all other radiosensitivity parameters were assumed to stay constant. Thus, the RBE cannot be predicted by the α / β -ratio alone. Conclusions : Although there is no direct correlation between the proton RBE and the parameters describing the x-ray survival curve, the track-structure model predicts a tendency for late-responding tissues (low α / β) to have higher RBE values than early-responding tissues (high α / β) . These calculations reinforce the experimental findings, but also strongly suggest that there are circumstances in which the tendency for RBE to increase with increasing α / β does not occur, or even could be reversed.

Induction of apoptosis by beta radiation from tritium compounds in mouse embryonic brain cells.

Induction of apoptosis by tritium exposure was investigated in both cultured embryonic mid brain cells and brain sections of embryos and of newborns in mice. In the cultures of mid brain cells, addition of methyl-3H-thymidine (3H-TdR) (21 kBq mL(-1)) and tritiated water (5.616 MBq mL(-1)) induced late appearances and low percentages of apoptosis when compared to x-irradiation at the ID50 dose, the inhibitory dose that reduced cellular differentiation by 50% of the control. A significant increase in p53 protein was detected about 2 h before the marked appearance of apoptosis. The pregnant mice were given an intraperitoneal injection of tritiated water at the concentration of 481.8 kBq g(-1) of body weight on gestation day 12.5, by which treatment behavioral changes in the offspring occurred. Increased apoptotic cells were observed in the neural tube of embryos from 1 d after the injection to 1 wk postnatal age. Apoptosis induced by x-rays appeared 2 h after irradiation, with a peak at 4 h. Increase of apoptotic cells was also found in the brain cortexes of newborns. The percentage of apoptosis in the brain was higher in the prenatal tritiated water exposed mice than in the prenatal x-irradiated mice. Possible mechanisms on apoptosis and its relation to the higher relative biological effectiveness value of tritium beta-rays are discussed.

Biological effects of hepatoma cells irradiated by 25MeV/u(40)Ar(14+).

Radiotherapy was initiated when Grubbe treated tumor with X-rays in 1896[1]. Afterwards, radioisotopes such as Ra and Rn, were used for clinical diagnosis and treatment. Basic researches on the biological effects of X-rays, γ-rays, fast neutron, and so on discovered that damages to mammalian cells induced by high-LET irradiation were more serious than that by low-LET[2]. Because of their low oxygen enhancement ratio (OER) and high relative biological effectiveness (RBE), heavy ions can kill carcinoma cells efficiently[3], among which about 5%-20% was hypoxia. There was a Bragg peak along the energy deposition of heavy ions, so that more dose could reach to the tumor while less to the normal tissues[4]. Therefore, heavy ion beam is believed to play an important role in the future in the radiotherapy for tumors. The treatment with heavy ion beam has been studied and put into clinical practice since the 1970s in America and since 1994 in Japan. But in our country, this research is still in its initial stage. This is our preliminary report on the dose--response and fractionated irradiation with 25MeV/u 40Ar14+ in human hepatoma SMMC-7721 cells.

Effects of accelerated carbon-ions on growth inhibition of transplantable human esophageal cancer in nude mice

We have studied the effectiveness of 290 MeV/u carbon-ion (C-) beams (linear energy transfer (LET) of 70 keV/mm) and 200 kVp X-rays on tumor growth inhibition as an in vivo model for radiotherapy of cancer. We measured the size of tumor growth of transplantable human esophageal cancer in nude mice after radiation with C-beams and compared this with X-rays as the control. A significant inhibition of tumor growth was observed by C-beams as compared with X-rays. The relative biological effectiveness (RBE) of C-beams against X-rays was 2.02. Histopathological studies showed that C-beams at 20 Gy induced prominent necrosis in the central region and multinucleate giant cells and inflammatory cells in peripheral regions of the tumor, whereas X-rays at 20 Gy induced only mild necrosis. The high RBE of C-beams obtained in this study provides in vivo evidence that C-beams are more effective than conventional X-rays for radiotherapy of cancer.

RBE for the induction of apoptosis in human peripheral lymphocytes exposed in vitro to high-LET radiation generated by accelerated nitrogen ions

Purpose: To investigate the relative biological effectiveness (RBE) of accelerated nitrogen ions (32-45 MeV/u) compared with 137Cs gamma -rays for the induction of apoptosis in G lymphocytes. 0 Materials and methods: Human peripheral G lymphocytes were 0 exposed in vitro to doses up to 3 Gy. RBE for the induction of apoptosis was studied at different times after irradiation (0, 24, 48 and 72 h) with the use of three different methods: (1) morphological characterization of apoptotic cells after fluorescence staining; (2) cell size distribution analysis of the cell population to detect apoptotic bodies; and (3) electrophoretic analysis of DNA to detect 'DNA-ladders'. Results: RBE values in the range of 1.3-3.0 were obtained from the linear components of the dose-response curves. The variation in RBE was primarily dependent on post-irradiation time, where the highest RBE values were obtained after 48 h. The three different techniques used for analysis of apoptosis gave similar results. The significantly increased RBE was also seen as an earlier appearance of DNA-ladders, as well as a more rapid disappearance of the total number of viable cells. Conclusions: These results show that nitrogen ions of high linear energy transfer (LET) produce RBE 1.0 and induce a faster apoptotic response as compared with gamma -photons of low-LET radiation.

Neutron RBEs for cytopenia and repopulation of stroma and hematopoietic stem cells: mathematical models of marrow cell kinetics.

The objectives of this study were to (a) extend previous bone-marrow cell kinetics models that have been published for ionizing photons to include neutron radiations, and (b) provide Relative Biological Effectiveness (RBE) values for time-specific cell killing (cytopenia) and compensatory cellular proliferation (repopulation in response to toxic injury) for neutron doses ranging from 0.01 to 4.5 Gy delivered uniformly over one minute, hour, day, week, and month. RBEs for cytopenia of a cell lineage were based on ratios of protocol-specific doses that determined the same cell population nadir, whereas the RBEs for repopulation of a lineage were based on the ratios of protocol-specific doses that corresponded to the same total number of cells killed over the radiation treatments, and which should be replaced for long-term survival of the animal. Time-dependent RBEs were computed for neutron exposures relative to the effect of 60Co gamma rays given as a prompt dose. By the use of these RBE factors, low or variable dose rates, dose fractionations given over long periods of time, and different protocols involving several radiation qualities can be converted realistically, and by standard convention, into an equivalent dose of a reference radiation comprised of x or gamma rays given either as a pulse or at any other reference dose rate for which risk information based on epidemiological or animal dose-response data are available. For stromal tissues irradiated by fission neutrons, time-dependent RBEs for cytopenia were computed to range from 4.24 to 0.70 and RBEs for repopulation varied from a high of 6.88 to a low of 2.24. For hematopoietic stem cells irradiated by fission neutrons, time-dependent RBEs for cytopenia were computed to range from 5.02 to 0.22 and RBEs for repopulation varied from a high of 5.02 to a low of 1.98. RBEs based on tissue-kerma-free-in-air would be about twofold lower for isotropic cloud or rotational exposure geometries because marrow dose from isotropic neutron fields suffer factor-of-two greater attenuation than the gamma doses from gamma photons. For certain doses and dose rates, the RBE values computed for compensatory cellular proliferation clearly demonstrate the behavior that is commonly referred to as an inverse dose-rate effect, i.e., protraction of exposure may-under certain conditions-increase the magnitude of the dose response. Furthermore, because of non-linear rates for repair and repopulation, the highest RBEs are not necessarily found for the lowest doses nor the lowest RBEs always found at the highest doses.

Biokinetics and dosimetry of chromium, cobalt, hydrogen, iron and zinc radionuclides in male reproductive tissues of the rat

. Following intravenous administration to male rats, the uptake and retention by reproductive tissues of chromium-51, cobalt-57, iron-59, zinc-65 and tritium has been studied for up to 28 days. Chromium-51, 57Co, 59Fe and 3H were not or only transiently accumulated in gonads or accessory sex glands at concentrations greater than whole body concentrations. However, 65Zn was concentrated in the dorsolateral region of the prostate gland and autoradiography showed preferential uptake by epithelial cells and lumen of glands. When combined with other information available from the literature, this data would suggest that current models adequately describe the biokinetics of chromium, cobalt, iron and tritium in the prostate and testes and zinc in the testes. Uptake of zinc by the prostate would appear to be best described by an average value of 0.1% and a conservative value of 0.5%. Allowing for greater uptake of zinc (0.5%) by the prostate, after inhalation of 65Zn in a soluble form, increases prostate dose by about 3 fold compared to current models. The pessimistic assumptions of a higher relative biological effectiveness (20) for all Auger emissions from 65Zn in cell nuclei and a heterogeneous distribution of 65Zn to sensitive cells in the prostate increases prostate dose by a further factor of 9. Even on the basis of these cautious estimates, occupational exposures to radioisotopes of these elements do not explain the excess of prostate cancer reported amongst some nuclear workers.

Chromosome Aberrations in Human Fibroblasts Induced by Monoenergetic Neutrons. I. Relative Biological Effectiveness

The relative biological effectiveness (RBE) of neutrons for many biological end points varies with neutron energy. To test the hypothesis that the RBE of neutrons varies with respect to their energy for chromosome aberrations in a cell system that does not face interphase death, we studied the yield of chromosome aberrations induced by monoenergetic neutrons in normal human fibroblasts at the first mitosis postirradiation. Monoenergetic neutrons at 0.22, 0.34, 0.43, 1, 5.9 and 13.6 MeV were generated at the Accelerator Facility of the Center for Radiological Research, Columbia University, and were used to irradiate plateau-phase fibroblasts at low absorbed doses from 0.3 to 1.2 Gy at a low dose rate. The reference low-LET, low-dose-rate radiation was 137Cs-gamma rays (0.66 MeV). A linear dose response (Y = alphaD) for chromosome aberrations was obtained for all monoenergetic neutrons and for the gamma rays. The yield of chromosome aberrations per unit dose was high at low neutron energies (0.22, 0.34 and 0.43 MeV) with a gradual decline with the increase in neutron energy. Maximum RBE (RBEm) values varied for the different types of chromosome aberrations. The highest RBE (24.3) for 0.22 and 0.43 MeV neutrons was observed for intrachromosomal deletions, a category of chromosomal change common in solid tumors. Even for the 13.6 MeV neutrons the RBEm (11.1) exceeded 10. These results show that the RBE of neutrons varies with neutron energy and that RBEs are dissimilar between different types of asymmetric chromosome aberrations and suggest that the radiation weighting factors applicable to low-energy neutrons need firmer delineation. This latter may best be attained with neutrons of well-defined energies. This would enable integrations of appropriate quality factors with measured radiation fields, such as those in high-altitude Earth atmosphere. The introduction of commercial flights at high altitude could result in many more individuals being exposed to neutrons than occurs in terrestrial workers, emphasizing the necessity for better-defined estimates of risk.

The Present System of Quantities and Units for Radiation Protection

The International Commission on Radiation Units and Measurements has over the last decade developed operational quantities, the ambient, directional and personal dose equivalent, suitable for the measurement of radiation fields in a variety of circumstances. Experience with the use of these quantities to represent the dose limitation quantities defined by the International Commission on Radiological Protection in 1977 has been an important part of recent radiation protection metrology. The definition by International Commission on Radiological Protection in 1991 of new limitation quantities, the equivalent dose and the effective dose has necessitated a redirection of this work. The metrology field has made good progress, however. It has found that for photons, at least above 50 keV, the effective dose can be measured by the ambient dose equivalent about as well as the former effective dose equivalent. Unfortunately, for neutrons the existing and already quite severe complications have been made somewhat worse by the new quantities although not any worse in the important region between 0.1 and 1 MeV. Neutron measurements over a broad energy range are the subject of extensive evaluation and some new suggestions as the metrology field wrestles with these problems. Values of wR constitute an important part of the International Commission on Radiological Protection recommendations. A brief history of the development of higher relative biological effectiveness values for fission neutrons and alpha particles leading to the selection of 20 for wR in each case, is provided.

On the Relative Biological Effectiveness of Alpha-Particle Irradiation with Respect to Hemopoietic Tissue

Recently Jiang et al. reported that a-particle irradiation resulting from plutonium-239 contamination in utero demonstrated, on long-term hemopoiesis, an extremely high relative biological effectiveness (RBE) compared to y irradiation (1). RBE values of 250 to 360 were estimated by comparing the perturbation in the number and spatial distribution of multipotent hemopoietic spleen colony-forming units (CFU-S) in the femora of adult murine offspring of mothers that had been contaminated with plutonium-239 at 13 days gestation with those after continuous external y irradiation of the pregnant female from 13 days gestation to birth. Thirty becquerels/gram plutonium-239 injected into the mother was estimated to give an average dose of 10 to 14 mGy to the fetal liver of her offspring in the 6 days before giving birth. Continuous y irradiation to a total dose of 3.6 Gy over the same 6 days was required to induce a comparable amount of long-term damage. In those experiments, RBE was determined using a range of y-ray doses compared to a single dose of aparticle contamination. Our conclusions, however, have since been questioned on the grounds that nothing was known of the dose response to plutonium-239. We do, in fact, have the appropriate information regarding the dose response for a-particle contamination as illustrated below.

RBE for carcinogenesis following exposure to high LET radiation.

Stochastic radiation effects following exposure to heavy ions and other high linear energy transfer (LET) radiation in space are a matter of concern when the long-term consequences of space flights are considered. This paper is an overview of the relevant literature, emphasizing uncertainties entailed from estimates of relative biological effectiveness (RBE) for different experiment endpoints, making the choice of a single weighting factor for the prediction of cancer risk in man extremely difficult. Life-span-shortening studies in mice exposed to heavy ions and ongoing large-scale experiments in monkeys exposed to protons suggest that RBEs for all cancers are lower than 5. This does not exclude a much higher RBE for rare tumors such as brain tumors in monkeys or promoted Harderian gland tumours in mice at LET >80 keV/mu m. Skin cancer studies in rats exposed to neon or argon resulted in similar RBE. Exposure to fission neutrons led to high RBE in all species, not excluding values much higher than 20 for specific cancers such as lung tumors in mice and all cancers in rats. The estimate of maximal RBE is, however, extremely dependent on the hypothesis made on the shape of the dose-response curves in the lower range of doses. These results suggest that neutrons may be the most hazardous component of high-LET radiation. There is only limited evidence from cancer experiments that LET >150 keV/mu m results in highly decreased efficiency, but this has been found for bone cancer induction following exposure to fission fragments.

Effects of sublethal irradiation with helium ions (300 MeV/nucleon) on basic hematological parameters of mice

The aim of the experiment was to obtain new knowledge on the biological effectiveness of high-energy (300 MeV/nucleon) helium ions, which represent a part of the spectrum of cosmic rays. Male (CBA × C57BL)F 1 mice, 4 months old, were exposed to a dose of 4 Gy helium ions (exposure rate 0.05 Gy/min). As a comparative standard irradiation the same dose of 4 Gy of 137Cs gamma-rays (exposure rate 0.07 Gy/min) was used. Material sampling was performed 6–8 h, 4 days and 9 days after irradiation for both experimental groups mentioned above. There were 7 animals in each group including the control group of non-irradiated mice. Eight basic hematological parameters of peripheral blood, bone marrow, spleen and thymus were studied. On day 4 after the irradiation with helium ions, the values of leukocyte counts in peripheral blood, bone marrow cellularity and spleen cellularity were reduced to about 10% of the respective control values while the decline after irradiation with gamma-rays amounted to about 50%. These and other results presented reflect a high relative biological effectiveness of 300 MeV/nucleon helium ions.

Sites of strand breakage in DNA irradiated by fast neutrons

Therapeutic fast neutrons are densely ionizing particles, with a high relative biological effectiveness relative to 60Co γ rays (RBE) and a low oxygen enhancement ratio (OER). The molecular basis of their properties is not yet entirely understood. In a previous work, we have shown that neutrons induce a different number of DNA frank strand breaks as compared to γ photons, and we have revealed the presence of breaks due to the direct effects of neutrons. In the present work, we searched for eventual differences in the chemical nature of the attacked sites in DNA irradiated in oxygenated diluted solution. We compare our results with neutrons to those previously reported by other authors using γ- or X-rays. Using sequencing gel electrophoresis of short natural DNA restriction fragments, or synthetic oligonucleotides, we have shown that, in the case of neutrons, the attack occurs with almost the same probability, at each nucleotide, as reported for γ- and X-rays. The doubling of bands in the bottom of gels shows the presence of two types of termini, the 3′-phosphate and the 3′-phosphoglycolate. Upon neutron irradiation, the 3′-phosphate end appears with a higher yield than the 3′-phosphoglycolate, whereas equal amounts were obtained with γ- or X-rays.

Indications of repair of radon-induced chromosome damage in human lymphocytes: an adaptive response induced by low doses of X-rays.

Naturally occurring radon is a relatively ubiquitous environmental carcinogen to which large numbers of people can be exposed over their lifetimes. The accumulation of radon in homes, therefore, has led to a large program to determine the effects of the densely ionizing alpha particles that are produced when radon decays. In human lymphocytes, low doses of X-rays can decrease the number of chromatid deletions induced by subsequent high doses of clastogens. This has been attributed to the induction of a repair mechanism by the low-dose exposures. Historically, chromosome aberrations induced by radon have been considered to be relatively irreparable. The present experiments, however, show that if human peripheral blood lymphocytes are irradiated with low doses of X-rays (2 cGy) at 48 hr of culture, before being exposed to radon at 72 hr of culture, the yield of chromatid deletions induced by radon is decreased by a factor of two. Furthermore, the numbers of aberrations per cell do not follow a Poisson distribution but are overdispersed, as might be expected because high-linear energy transfer (high LET) alpha particles have a high relative biological effectiveness compared to low-LET radiations such as X-rays or gamma rays. Pretreatment with a low dose of X-rays decreases the overdispersion and leads to a greater proportion of the cells having no aberrations, or lower numbers of aberrations, than is the case in cells exposed to radon alone.(ABSTRACT TRUNCATED AT 250 WORDS)