Effects of internal exposure to neutron-activated 56MnO2 powder on locomotor activity in rats.

At the detonation of the atomic bombing in Hiroshima and Nagasaki, a significant amount of radionuclides was produced by the neutron induced activation. The residual radiation from the explosion is crucial to the health risk of the people who entered these cities after the bombing and might have inhaled these radioactive materials. Because 56Mn is one of the major radionuclides produced in soil and have not been studied until now, we had conducted a series of experiments using rats to investigate the biological impacts of exposure of 56MnO2 particles. In these experiments, the rats' spontaneous locomotor activity was also assessed to examine the possible effects of 56Mn on their behavior. However, the locomotor activity data obtained from an individual experiment failed to identify radiation effects due to the large variation among animals and the small sample size. In the present study, all available data from our previous studies on 56MnO2 exposure (0.02-0.15 Gy of whole-body doses) as well as 60Co-γ exposure (at 2-5 Gy of whole-body doses) were pooled. Our statistical method, which takes into account individual differences and daily fluctuations, successfully identified a decrease in locomotor activity caused by 56MnO2 exposure, where the changes were gradual and reached the maximum reduction around 2 weeks after exposure. In contrast, exposure to 60Co-γ rays produced the highest decline of activity within one day. These results suggest that internal exposure to 56Mn at whole-body doses of even less than 0.15 Gy may have a long-lasting impact on locomotor activity.

Hepatic Gene Expression Changes in Rats Internally Exposed to Radioactive 56MnO2 Particles at Low Doses.

We have studied the biological effects of the internal exposure to radioactive manganese-56 dioxide (56MnO2), the major radioisotope dust found in soil after atomic bomb explosions. Our previous study of blood chemistry indicated a possible adverse effect of 56MnO2 on the liver. In the present study, we further examined the effects on the liver by determining changes in hepatic gene expressions. Male Wistar rats were exposed to 56MnO2 particles (three groups with the whole-body doses of 41, 90, and 100 mGy), stable MnO2 particles, or external 60Co γ-rays (2 Gy), and were examined together with the non-treated control group on postexposure day 3 and day 61. No histopathological changes were observed in the liver. The mRNA expression of a p53-related gene, the cyclin-dependent kinase inhibitor 1A, increased in 56MnO2 as well as in γ-ray irradiated groups on postexposure day 3 and day 61. The expression of a stress-responsive gene, nuclear factor κB, was also increased by 56MnO2 and γ-rays on postexposure day 3. However, the expression of cytokine genes (interleukin-6 or chemokine ligand 2) or fibrosis-related TGF-ß/Smad genes (Tgfb1, Smad3, or Smad4) was not altered by the exposure. Our data demonstrated that the internal exposure to 56MnO2 particles at less than 0.1 Gy significantly affected the short-term gene expressions in the liver in a similar manner with 2 Gy of external γ-irradiation. These changes may be adaptive responses because no changes occurred in cytokine or TGF-ß/Smad gene expressions.

Internal doses in experimental mice and rats following exposure to neutron-activated 56MnO2 powder: results of an international, multicenter study.

The experiment was performed in support of a Japanese initiative to investigate the biological effects of irradiation from residual neutron-activated radioactivity that resulted from the A-bombing. Radionuclide 56Mn (T1/2 = 2.58 h) is one of the main neutron-activated emitters during the first hours after neutron activation of soil dust particles. In our previous studies (2016-2017) related to irradiation of male Wistar rats after dispersion of 56MnO2 powder, the internal doses in rats were found to be very inhomogeneous: distribution of doses among different organs ranged from 1.3 Gy in small intestine to less than 0.0015 Gy in some of the other organs. Internal doses in the lungs ranged from 0.03 to 0.1 Gy. The essential pathological changes were found in lung tissue of rats despite a low level of irradiation. In the present study, the dosimetry investigations were extended: internal doses in experimental mice and rats were estimated for various activity levels of dispersed neutron-activated 56MnO2 powder. The following findings were noted: (a) internal radiation doses in mice were several times higher in comparison with rats under similar conditions of exposure to 56MnO2 powder. (b) When 2.74 × 108 Bq of 56MnO2 powder was dispersed over mice, doses of internal irradiation ranged from 0.81 to 4.5 Gy in the gastrointestinal tract (small intestine, stomach, large intestine), from 0.096 to 0.14 Gy in lungs, and doses in skin and eyes ranged from 0.29 to 0.42 Gy and from 0.12 to 0.16 Gy, respectively. Internal radiation doses in other organs of mice were much lower. (c) Internal radiation doses were significantly lower in organs of rats with the same activity of exposure to 56MnO2 powder (2.74 × 108 Bq): 0.09, 0.17, 0.29, and 0.025 Gy in stomach, small intestine, large intestine, and lungs, respectively. (d) Doses of internal irradiation in organs of rats and mice were two to four times higher when they were exposed to 8.0 × 108 Bq of 56MnO2 (in comparison with exposure to 2.74 × 108 Bq of 56MnO2). (e) Internal radiation doses in organs of mice were 7-14 times lower with the lowest 56MnO2 amount (8.0 × 107 Bq) in comparison with the highest amount, 8.0 × 108 Bq, of dispersed 56MnO2 powder. The data obtained will be used for interpretation of biological effects in experimental mice and rats that result from dispersion of various levels of neutron-activated 56MnO2 powder, which is the subject of separate studies.

Effects of Internal Exposure to 56MnO2 Powder on Blood Parameters in Rats.

OBJECTIVE: The pathological effects of internal exposure to manganese dioxide-56 (56MnO2) radioisotope particles have been previously examined in rats. Here we further examine the effects of 56MnO2, focusing on changes in blood parameters. MATERIALS AND METHODS: Ten-week-old male Wistar rats were exposed to 3 doses of neutron-activated 56MnO2 powder, nonradioactive MnO2 powder, or external 60Co γ-rays (1 Gy, whole body). On days 3 and 61 postexposure, the animals were necropsied to measure organ weights and clinical blood parameters, including red blood cell and white blood cell counts; concentrations of calcium, phosphorus, potassium, and sodium; and levels of alanine aminotransferase (ALT), aspartate aminotransferase, amylase, creatinine, urea, total protein, albumin, triglycerides, high density lipoprotein, total cholesterol, and glucose. RESULTS: In the 56MnO2-exposed animals, accumulated doses were found to be highest in the gastrointestinal tract, followed by the skin and lungs, with whole-body doses ranging from 41 to 100 mGy. There were no 56MnO2 exposure-related changes in body weights or relative organ weights. The ALT level decreased on day 3 and then significantly increased on day 61 in the 56MnO2-exposed groups. There were no exposure-related changes in any other blood parameters. CONCLUSION: Although the internal doses were less than 100 mGy, internal exposure of 56MnO2 powder showed significant biological impacts.

Internal exposure to neutron-activated 56Mn dioxide powder in Wistar rats-Part 2: pathological effects.

To fully understand the radiation effects of the atomic bombing of Hiroshima and Nagasaki among the survivors, radiation from neutron-induced radioisotopes in soil and other materials should be considered in addition to the initial radiation directly received from the bombs. This might be important for evaluating the radiation risks to the people who moved to these cities soon after the detonations and probably inhaled activated radioactive "dust." Manganese-56 is known to be one of the dominant radioisotopes produced in soil by neutrons. Due to its short physical half-life, 56Mn emits residual radiation during the first hours after explosion. Hence, the biological effects of internal exposure of Wistar rats to 56Mn were investigated in the present study. MnO2 powder was activated by a neutron beam to produce radioactive 56Mn. Rats were divided into four groups: those exposed to 56Mn, to non-radioactive Mn, to 60Co γ rays (2 Gy, whole body), and those not exposed to any additional radiation (control). On days 3, 14, and 60 after exposure, the animals were killed and major organs were dissected and subjected to histopathological analysis. As described in more detail by an accompanying publication, the highest internal radiation dose was observed in the digestive system of the rats, followed by the lungs. It was found that the number of mitotic cells increased in the small intestine on day 3 after 56Mn and 60Co exposure, and this change persisted only in 56Mn-exposed animals. Lung tissue was severely damaged only by exposure to 56Mn, despite a rather low radiation dose (less than 0.1 Gy). These data suggest that internal exposure to 56Mn has a significant biological impact on the lungs and small intestine.