Dataset Information

Effects of Radioactive ⁵⁶MnO₂ Particle Inhalation on Mouse Lungs: A Comparison between C57BL and BALB/c.

ABSTRACT: The effects of residual radiation from atomic bombs have been considered to be minimal because of its low levels of external radioactivity. However, studies involving atomic bomb survivors exposed to only residual radiation in Hiroshima and Nagasaki have indicated possible adverse health effects. Thus, we investigated the biological effects of radioactive dust of manganese dioxide 56 (⁵⁶MnO₂), a major radioisotope formed in soil by neutron beams from a bomb. Previously, we investigated C57BL mice exposed to ⁵⁶MnO₂ and found pulmonary gene expression changes despite low radiation doses. In this study, we examined the effects in a radiation-sensitive strain of mice, BALB/c, and compared them with those in C57BL mice. The animals were exposed to ⁵⁶MnO₂ particles at two radioactivity levels and examined 3 and 65 days after exposure. The mRNA expression of pulmonary pathophysiology markers, including Aqp1, Aqp5, and Smad7, and radiation-sensitive genes, including Bax, Phlda3, and Faim3, was determined in the lungs. The radiation doses absorbed in the lungs ranged from 110 to 380 mGy; no significant difference was observed between the two strains. No exposure-related pathological changes were observed in the lungs of any group. However, the mRNA expression of Aqp1 was significantly elevated in C57BL mice but not in BALB/c mice 65 days after exposure, whereas no changes were observed in external γ-rays (2 Gy) in either strain. In contrast, Faim3, a radiation-dependently downregulated gene, was reduced by ⁵⁶MnO₂ exposure in BALB/c mice but not in C57BL mice. These data demonstrate that inhalation exposure to ⁵⁶MnO₂ affected the expression of pulmonary genes at doses <380 mGy, which is comparable to 2 Gy of external γ-irradiation, whereas the responses differed between the two mouse strains.

SUBMITTER: Abishev Z

PROVIDER: S-EPMC10743477 | biostudies-literature | 2023 Dec

REPOSITORIES: biostudies-literature

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Effects of Radioactive 56MnO2 Particle Inhalation on Mouse Lungs: A Comparison between C57BL and BALB/c.

Abishev Zhaslan Z Ruslanova Bakhyt B Apbassova Saulesh S Shabdarbayeva Dariya D Chaizhunussova Nailya N Dyusupov Altai A Azhimkhanov Almas A Zhumadilov Kassym K Stepanenko Valeriy V Ivanov Sergey S Shegay Peter P Kaprin Andrey A Hoshi Masaharu M Fujimoto Nariaki N

International journal of molecular sciences 20231218 24

The effects of residual radiation from atomic bombs have been considered to be minimal because of its low levels of external radioactivity. However, studies involving atomic bomb survivors exposed to only residual radiation in Hiroshima and Nagasaki have indicated possible adverse health effects. Thus, we investigated the biological effects of radioactive dust of manganese dioxide 56 (56MnO2), a major radioisotope formed in soil by neutron beams from a bomb. Previously, we ...[more]

PMID: 38139433

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Project description:BackgroundAn important aspect of nanomaterial (NM) risk assessment is establishing relationships between physicochemical properties and key events governing the toxicological pathway leading to adverse outcomes. The difficulty of NM grouping can be simplified if the most toxicologically relevant dose metric is used to assess the toxicological dose-response. Here, we thoroughly investigated the relationship between acute and chronic inflammation (based on polymorphonuclear neutrophil influx (% PMN) in lung bronchoalveolar lavage) and the retained surface area in the lung. Inhalation studies were performed in rats with three classes of NMs: titanium dioxides (TiO2) and carbon blacks (CB) as poorly soluble particles of low toxicity (PSLT), and multiwall carbon nanotubes (MWCNTs). We compared our results to published data from nearly 30 rigorously selected articles.ResultsThis analysis combined data specially generated for this work on three benchmark materials - TiO2 P25, the CB Printex-90 and the MWCNT MWNT-7 - following subacute (4-week) inhalation with published data relating to acute (1-week) to subchronic (13-week) inhalation exposure to the classes of NMs considered. Short and long post-exposure recovery times (immediately after exposure up to more than 6 months) allowed us to examine both acute and chronic inflammation. A dose-response relationship across short-term and long-term studies was revealed linking pulmonary retained surface area dose (measured or estimated) and % PMN. This relationship takes the form of sigmoid curves, and is independent of the post-exposure time. Curve fitting equations depended on the class of NM considered, and sometimes on the duration of exposure. Based on retained surface area, long and thick MWCNTs (few hundred nm long with an aspect ratio greater than 25) had a higher inflammatory potency with 5 cm2/g lung sufficient to trigger an inflammatory response (at 6% PMN), whereas retained surfaces greater than 150 cm2/g lung were required for PSLT.ConclusionsRetained surface area is a useful metric for hazard grouping purposes. This metric would apply to both micrometric and nanometric materials, and could obviate the need for direct measurement in the lung. Indeed, it could alternatively be estimated from dosimetry models using the aerosol parameters (rigorously determined following a well-defined aerosol characterization strategy).

Project description:Astronauts during interplanetary missions will be exposed to galactic cosmic radiation, including charged particles like 56Fe. Most preclinical studies with mature, "astronaut-aged" rodents suggest space radiation diminishes performance in classical hippocampal- and prefrontal cortex-dependent tasks. However, a rodent cognitive touchscreen battery unexpectedly revealed 56Fe radiation improves the performance of C57BL/6J male mice in a hippocampal-dependent task (discrimination learning) without changing performance in a striatal-dependent task (rule-based learning). As there are conflicting results on whether the female rodent brain is preferentially injured by or resistant to charged particle exposure, and as the proportion of female vs. male astronauts is increasing, further study on how charged particles influence the touchscreen cognitive performance of female mice is warranted. We hypothesized that, similar to mature male mice, mature female C57BL/6J mice exposed to fractionated whole-body 56Fe irradiation (3 × 6.7cGy 56Fe over 5 days, 600 MeV/n) would improve performance vs. Sham conditions in touchscreen tasks relevant to hippocampal and prefrontal cortical function [e.g., location discrimination reversal (LDR) and extinction, respectively]. In LDR, 56Fe female mice more accurately discriminated two discrete conditioned stimuli relative to Sham mice, suggesting improved hippocampal function. However, 56Fe and Sham female mice acquired a new simple stimulus-response behavior and extinguished this acquired behavior at similar rates, suggesting similar prefrontal cortical function. Based on prior work on multiple memory systems, we next tested whether improved hippocampal-dependent function (discrimination learning) came at the expense of striatal stimulus-response rule-based habit learning (visuomotor conditional learning). Interestingly, 56Fe female mice took more days to reach criteria in this striatal-dependent rule-based test relative to Sham mice. Together, our data support the idea of competition between memory systems, as an 56Fe-induced decrease in striatal-based learning is associated with enhanced hippocampal-based learning. These data emphasize the power of using a touchscreen-based battery to advance our understanding of the effects of space radiation on mission critical cognitive function in females, and underscore the importance of preclinical space radiation risk studies measuring multiple cognitive processes, thereby preventing NASA's risk assessments from being based on a single cognitive domain.

Dataset Information

Effects of Radioactive ⁵⁶MnO₂ Particle Inhalation on Mouse Lungs: A Comparison between C57BL and BALB/c.

Publications

Effects of Radioactive <sup>56</sup>MnO<sub>2</sub> Particle Inhalation on Mouse Lungs: A Comparison between C57BL and BALB/c.

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