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Background: Clonogenicity gives important information about the cellular reproductive potential following ionizing irradiation, but an abortive colony that fails to continue to grow remains poorly characterized. It was recently reported that the fraction of abortive colonies increases with increasing dose. Thus, we set out to investigate the production kinetics of abortive colonies using a model of branching processes., Methodology/principal Findings: We firstly plotted the experimentally determined colony size distribution of abortive colonies in irradiated normal human fibroblasts, and found the linear relationship on the log-linear or log-log plot. By applying the simple model of branching processes to the linear relationship, we found the persistent reproductive cell death (RCD) over several generations following irradiation. To verify the estimated probability of RCD, abortive colony size distribution (≤ 15 cells) and the surviving fraction were simulated by the Monte Carlo computational approach for colony expansion. Parameters estimated from the log-log fit demonstrated the good performance in both simulations than those from the log-linear fit. Radiation-induced RCD, i.e. excess probability, lasted over 16 generations and mainly consisted of two components in the early (<3 generations) and late phases. Intriguingly, the survival curve was sensitive to the excess probability over 5 generations, whereas abortive colony size distribution was robust against it. These results suggest that, whereas short-term RCD is critical to the abortive colony size distribution, long-lasting RCD is important for the dose response of the surviving fraction., Conclusions/significance: Our present model provides a single framework for understanding the behavior of primary cell colonies in culture following irradiation.

Learning impairment following ionizing radiation (IR) exposure is an important potential risk in manned space missions. We previously reported the modulatory effects of IR on salt chemotaxis learning in Caenorhabditis elegans. However, little is known about the effects of IR on the functional relationship in the nervous system. In the present study, we investigated the effects of gamma-ray exposure on the relationship between locomotion and salt chemotaxis learning behavior. We found that effects of pre-learning irradiation on locomotion were significantly correlated with the salt chemotaxis learning performance, whereas locomotion was not directly related to chemotaxis to NaCl. On the other hand, locomotion was positively correlated with salt chemotaxis of animals which were irradiated during learning, and the correlation disappeared with increasing doses. These results suggest an indirect relationship between locomotion and salt chemotaxis learning in C. elegans, and that IR inhibits the innate relationship between locomotion and chemotaxis, which is related to salt chemotaxis learning conditioning of C. elegans.

Ionizing radiation (IR) is known to impair learning by suppressing adult neurogenesis in the hippocampus. However, in a mature nervous system, IR-induced functional alterations that are independent of neurogenesis remain largely unknown. In the present study, we analyzed the effects of IR on a food-NaCl associative learning paradigm of adult Caenorhabditis elegans that does not undergo neurogenesis. We observed that a decrease in chemotaxis toward NaCl occurs only after combined starvation and exposure to NaCl. Exposure to IR induced an additional decrease in chemotaxis immediately after an acute dose in the transition stage of the food-NaCl associative learning. Strikingly, chronic irradiation induced negative chemotaxis in the exposed animals, i.e., the primary avoidance response. IR-induced additional decreases in chemotaxis after acute and chronic irradiation were significantly suppressed in the gpc-1 mutant, which was defective in GPC-1 (one of the two gamma subunits of the heterotrimeric G-protein). Chemotaxis to cAMP, but not to lysine and benzaldehyde, was influenced by IR during the food-NaCl associative learning. Our novel findings suggest that IR behaves as a modulator in the food-NaCl associative learning via C. elegans GPC-1 and a specific neuronal network and may shed light on the modulatory effect of IR on learning.

Extracellular DNA is omnipresent in aquatic environments and is thought to be a genetic material for horizontal gene transformation between microorganisms. We studied the impact of gamma irradiation on the transformation efficiency (transformants number per ng of DNA per ml) of extracellular DNA. Plasmid pEGFP as a model extracellular DNA was irradiated by gamma rays. The transformation efficiency decreased with the increase in radiation dose. A total dose of 10Gy is normally not lethal for microorganisms but certainly affects the transformation efficiency of extracellular DNA. The decrease in the efficiency would be induced by strand breaks of extracellular DNA because the yield of both single-strand breaks (SSBs) and double-strand breaks (DSBs) increased with the increase in radiation dose. The relative transformation efficiency of SSBs and DSBs to that of covalently closed circles (CCCs) was 30.3% and 0.2%, respectively. This impact on natural transformation suggests an inability of microorganisms to acquire new characteristics which should be normally acquired.

Purpose: Tardigrades are known to survive high doses of ionizing radiation. However, there have been no reports about radiation effects in tardigrades under culture conditions. In this study, we investigated tolerance of the tardigrade, Milnesium tardigradum, against gamma-rays and heavy ions by determining short-term or long-term survival, and reproductive ability after irradiation., Materials and Methods: Hydrated and anhydrobiotic animals were exposed to gamma-rays (1000 - 7000 Gy) or heavy ions (1000 - 8000 Gy) to evaluate short-term survival at 2, 24 and 48 h post-irradiation. Long-term survival and reproduction were observed up to 31 days after irradiation with gamma-rays (1000 - 4000 Gy)., Results: At 48 h after irradiation, median lethal doses were 5000 Gy (gamma-rays) and 6200 Gy (heavy ions) in hydrated animals, and 4400 Gy (gamma-rays) and 5200 Gy (heavy ions) in anhydrobiotic ones. Gamma-irradiation shortened average life span in a dose-dependent manner both in hydrated and anhydrobiotic groups. No irradiated animals laid eggs with one exception in which a hydrated animal irradiated with 2000 Gy of gamma-rays laid 3 eggs, and those eggs failed to hatch, whereas eggs produced by non-irradiated animals hatched successfully., Conclusion: M. tardigradum survives high doses of ionizing radiation in both hydrated and anhydrobiotic states, but irradiation with >1000 Gy makes them sterile.

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.

The protective effects of Trolox on the inhibition of negative gravitaxis in Euglena gracilis exposed to 200 Gy 60Co gamma-rays were examined using different concentrations (1, 10 and 100 microM). The orientation precision of the negative gravitaxis was quantified using the r-value. A significant decrease in the r-value was observed in gamma-irradiated samples (0.18+/-0.03) compared to those of non-irradiated samples (0.47+/-0.03). There were no significant changes in the r-value of cells exposed to 200 Gy gamma-rays by the addition of 1 or 10 microM of Trolox. A significant increase (0.19) in the r-value of cells exposed to 200 Gy with 100 microM Trolox was observed. The results indicates that Trolox at a concentration of 100 microM protects negative gravitaxis against 60Co gamma-ray irradiation at a dose of 200 Gy. It also suggests that the negative gravitaxis of Euglena gracilis is affected by free radicals.

Objective: To study the effects of gamma-ray irradiation on carbon fixation (Specific production rate: SPR), CO2 utilization efficiency (CUE) and electron transfer rate (ETR) in the photosynthetic flagellate Euglena gracilis strain Z in a dose-response dependent manner., Methods: Euglena cells were cultured in an inorganic nutrient medium containing ammonium chloride or proteose peptone. Cells were exposed to gamma-ray at 5 doses (0, 100, 250, 350, 500 Gy for water). Five days after irradiation, three photosynthetic activities were measured. SPR, which is a carbon uptake rate per unit carbon mass, was determined by 13C tracer methodology. CUE was evaluated using a relation of carbon isotope fractionation in Calvin cycle. ETR in photosystem II (PS II) was measured by a chlorophyll fluorescence analysis., Results: Even at a dose of 500 Gy, 80% of ETR of the non-irradiated control (0 Gy) was sustained, while SPR and CUE were about half the level in the non-irradiated control at 500 Gy. Furthermore, the dose response of ETR was considerably different from the others., Conclusion: Our findings suggest that not only PS II but also the Calvin cycle in the photosynthetic system is affected by gamma ray irradiation.

The effects of gamma-ray and high energy carbon ion irradiation on the swimming velocity of the photosynthetic flagellate Euglena gracilis strain Z were studied, focusing on a dose-effect relationship. Cells were exposed to 60Co gamma-rays at 6 doses of 10, 15, 20, 40, 100 and 200 Gy for water, and also to 290 MeV/amu carbon ions from the Heavy Ion Medical Accelerator in Chiba at 7 doses (5, 10, 15, 20, 50, 100 and 200 Gy for water). The swimming velocity was measured by a biomonitoring system, called ECOTOX. The swimming velocities of Euglena gracilis cells were significantly decreased by >40 Gy gamma-rays and >5 Gy carbon ions, respectively. The 50% effective doses for inhibition, 34 +/- 4 Gy (gamma-rays) and 13 +/- 1 Gy (290 MeV/amu carbon ions), were estimated from the best fit to data of the logistic model. The relative biological effectiveness (2.6 +/- 0.4) was calculated by the ratio of 50% effective doses. The inhibition of the swimming velocity of the cells irradiated with gamma-rays was still present after 3 days, while recovery of the swimming velocity was shown in the cells exposed to 290 MeV/amu carbon ions. It is suggested that ionizing radiation inhibits ATP production and/or increases frictional drag on beating of the flagellum, thus decreasing swimming velocity., (c2002 COSPAR. Published by Elsevier Science Ltd. All rights reserved.)