The relative biological effectiveness of 14.5-MeV neutrons for the induction of gene conversion and mutation in yeast

The relative biological effectiveness (RBE) and oxygen enhancement ratio (OER) were determined in the yeast Saccharomyces cerevisiae for the induction of gene conversion (the product of recombinational repair) and mutation (the product of error prone repair) by 14.5-MeV neutrons in comparison with 60Co gamma rays and 150 KVp X rays. Neutron irradiation in oxic or anoxic conditions induced significantly higher yields of convertants and mutants than sparsely ionizing radiations under the same conditions. RBEs for both gene conversion and mutation under anoxia were significantly higher than under oxic conditions. RBEs for mutant induction under anoxia were lower than the RBEs for gene conversion under the same conditions. The data support the hypothesis that the production of lesions leading to the genetic consequences of gene conversion and mutation differ in their dependence upon LET and the presence of oxygen during irradiation, and therefore the two DNA repair processes which produce these end points recognize, at least in part, different classes of damage.     

Experimental derivation of relative biological effectiveness of A-bomb neutrons in Hiroshima and Nagasaki and implications for risk assessment

Epidemiological data on the health effects of A-bomb radiation in Hiroshima and Nagasaki provide the framework for setting limits for radiation risk and radiological protection. However, uncertainty remains in the equivalent dose, because it is generally believed that direct derivation of the relative biological effectiveness (RBE) of neutrons from the epidemiological data on the survivors is difficult. To solve this problem, an alternative approach has been taken. The RBE of polyenergetic neutrons was determined for chromosome aberration formation in human lymphocytes irradiated in vitro, compared with published data for tumor induction in experimental animals, and validated using epidemiological data from A-bomb survivors. The RBE of fission neutrons was dependent on dose but was independent of the energy spectrum. The same RBE regimen was observed for lymphocyte chromosome aberrations and tumors in mice and rats. Used as a weighting factor for A-bomb survivors, this RBE system was superior in eliminating the city difference in chromosome aberration frequencies and cancer mortality. The revision of the equivalent dose of A-bomb radiation using DS02 weighted by this RBE system reduces the cancer risk by a factor of 0.7 compared with the current estimates using DS86, with neutrons weighted by a constant RBE of 10.     

The question of relative biological effectiveness and quality factor for auger emitters incorporated into proliferating mammalian cells

The problem of determining RBE values for Auger emitters incorporated into proliferating mammalian cells is examined. In general, the reference radiation plays a key role in obtaining experimental RBE values. Using survival of cultured Chinese hamster V79 cells as the experimental model, new data are provided regarding selection of a reference radiation for internal Auger emitters. These data show that gamma rays delivered acutely (137Cs) are more than twice as lethal as gamma rays delivered chronically with an exponentially decreasing dose rate (99mTc). The results confirm that the reference radiation should be delivered chronically in a manner consistent with the extended exposure received by the cells in the case of incorporated radionuclides. Through a direct comparison of the radiotoxicity of Auger emitters and alpha emitters, the high RBE values reported for DNA-bound Auger emitters are confirmed. These studies reveal that the DNA binding compound [125I]iododeoxyuridine (125IdU) is about 1.6 times more effective in killing V79 cells than 5.3 MeV alpha particles from intracellularly localized 210Po-citrate. In addition, toxicity studies with the radiochemicals 125IdU and [125]-iododeoxycytidine (125IdC) establish the equivalence of the radiosensitivity of thymine and cytosine base sites in the DNA. In view of these results, and information already available, the question of establishing quality factors for Auger emitters is considered. Finally, a method for calculation of the dose equivalent for internal Auger emitters is advanced.     

Relative biological effectiveness of fission neutrons for induction of micronucleus formation in mouse reticulocytes in vivo

Following whole-body irradiation of ICR mice with various doses of fission neutrons or X-rays, the frequency of micronuclei (MNs) in peripheral blood reticulocytes was measured at 12 h intervals beginning immediately after irradiation and ending at 72 h after irradiation. The resulting time-course curve of MN frequency had a clear peak 36 h after irradiation, irrespective of the type of radiation applied and the dose used. The MN frequency, averaged as the unweighted mean over the experimental time course, showed a linear increase with increasing dose of either fission neutrons or X-rays. The linear response to X-rays supports reported conclusion that induction of MN formation in reticulocytes is a dose-rate independent phenomenon. The relative biological effectiveness (RBE) of fission neutrons to X-rays for MN induction was estimated to be 1.9 +/- 0.3. This value is considerably lower than the RBE value of 4.6 +/- 0.5 reported for the same fission neutrons for induction of lymphocyte apoptosis in the thymus of ICR mice that represents dose-rate independent, one-track event. Based on these results, we propose that MNs increased in reticulocytes after irradiation mostly represent acentric fragments caused by single chromosome breaks, and that some confounding factor is operating in erythroblasts for the formation of aberrations from non-rejoining DNA double-strand breaks more severely after high-LET radiation than after low-LET radiation.     

Detrimental effect of fast neutrons on cultured immature rat hippocampal cells: relative biological effectiveness of in vitro cell death indices

This in vitro study compared the detrimental effect and relative biological effectiveness (RBE) of high-linear energy transfer (LET) fast neutrons on rat immature hippocampal cultured cells with those of low-LET γ rays. Immature hippocampal cells were exposed to fast neutrons or γ rays. Cytotoxicity and cell viability were analyzed using a lactate dehydrogenase (LDH)-release assay and a 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide (MTT) assay, respectively. The cytotoxicity and cell viability with fast neutrons or γ rays varied in a dose-dependent pattern. In the LDH release and MTT assay indices, the RBEs of fast neutrons were approximately 2.35 and 2.42, respectively. Fast neutrons markedly induced apoptotic changes in immature hippocampal cells with increased expression of active caspase-3 and cleaved poly(ADP-ribose) polymerase. Increased cytotoxicity and decreased cell viability in immature hippocampal cells were seen in a dose-dependent pattern after fast-neutron and γ irradiation. Fast neutrons have a higher RBE for cell death indices than γ rays.     

Distribution of the relative biological effectiveness of fast neutrons according to the depth of the irradiated tissue

A study was made of the dependence of relative biological effectiveness (RBE) and isoeffective dose of fast neutrons (produced by U-120 cyclotron) upon the depth of the exposed tissue. It was shown that the isoeffective dose and RBE vary significantly with the depth of the tissue-equivalent medium. The investigations were carried out with the purpose of improving the radiobiological and dosimetric techniques for the treatment of malignant tumors using a neutron beam from U-120 cyclotron.     

The relative biological effectiveness of low doses of 14 MeV neutrons in steady-state murine spermatogenesis as determined by flow cytometry

The relative biological effectiveness of 14 MeV neutrons in the low-dose range < or =1 Gy has been determined in differentiating and differentiated spermatogonia. Male NMRI mice were exposed to single doses of 2 cGy to 3 Gy of (60)Co gamma rays or neutrons. The ratios of testicular S-phase cells, 4c primary spermatocytes, and elongated spermatids were quantified by DNA flow cytometry 2 to 70 days after irradiation and were found to decrease. Histological samples and testis weight were analyzed in parallel. Doses of 2-5 cGy neutrons and 10-50 cGy gamma rays significantly (P<0.05) decreased the proportions of S-phase cells, spermatocytes and elongated spermatids at 4, 14 and 28 days postirradiation. For S-phase cells, the biphasic shape of the cell survival curves was described with a D(50) of 5 cGy neutrons. The D(50) for (60)Co gamma rays and the relative biological effectiveness could not be determined. The relative biological effectiveness of neutrons at 50% reductions of testis weight, primary spermatocytes, and elongated spermatids were 2.5, 10.0 and 6.1, respectively. This in vivo assay is interesting because of its sensitivity at dose ranges that are relevant for exposures in the environment, the workplace and radiotherapy.