measuring-dna-damage-repair-mouse-splenocytes-after-chronic-vivo

Measuring DNA Damage and Repair in Mouse Splenocytes After Chronic <em>In Vivo</em> Exposure to Very Low Doses of Beta- and Gamma-Radiation

Low dose radiation exposure may produce a variety of biological effects that are different in quantity and quality from the effects produced by high ...

Canadian Nuclear Laboratories

Polonium-210 ((210)Po) is one of the most toxic radionuclides and was used as a poison in the Alexander Litvinenko case. In this study of the metabolism of (210)Po in rats, volatile (210)Po in excreta was measured, filling a knowledge gap of the previous studies. Five rats were intravenously administrated with 2 kBq and another five with 10 kBq of (210)Po (citrate form). They were housed in a glass Metabowl system for 4 d following the administration. Volatile (210)Po from the excreta was collected in a trapping system filled with liquid scintillation cocktail and was measured by liquid scintillation counting. Results showed that the daily excretion of volatile (210)Po by the rats is in a very small percentage (0.002-0.009 %) of the administered amounts. However, if the administered amount is large, the excretion of volatile (210)Po can be significant.

Metabolism of 210Po in rats: volatile 210Po in excreta.

The metabolic formation of volatile (210)Po species in a rat that was intravenously administered with (210)Po-citrate was investigated in this study. A slurry of the faecal sample was prepared in water and was bubbled with nitrogen gas in a closed system. The discharged gas was passed through a trapping device filled with liquid scintillation cocktail in order to capture any volatile (210)Po species. The amount of (210)Po trapped in the scintillation cocktail was measured by a liquid scintillation analyser that provided evidence of the presence of volatile (210)Po species in the faeces. The presence of volatile (210)Po in the faeces indicates that the metabolic formation of volatile (210)Po is likely to occur in the gut due to bacterial activity. The amount of volatile (210)Po species was compared with the daily faecal excretion of (210)Po. After 2 h of bubbling, the volatile (210)Po collected from the faeces sample was found to be between 1.0 and 1.7 % of the daily faecal excretion for the 4 d following (210)Po-citrate administration.

Metabolism of 210Po in rats: volatile 210Po from faeces.

Daily excretions of ²¹⁰Po from rats via urine and faeces following i.v. administration of polonium citrate, from Day 2 to Day 5, were reported, together with retentions in tissues and organs on Day 5. Emphasis is given to the methods of measurement and data quality rather than to the discussion of the observations. The authors aim to contribute data for developing or refining the biokinetic model for ²¹⁰Po metabolism.

Biokinetics of ²¹⁰Po in rats: excretion via urine and faeces and retention in tissues and organs.

Current practice for radiation protection associated with (131)I therapy mainly focuses on external and internal exposure caused by physical contamination of the hospital staff, other patients and family members. However, if volatile (131)I is excreted by the treated patients, these individuals could also be exposed through inhalation of (131)I. This study quantifies the amount of volatile (131)I excreted by rats after intravenous administration of metaiodobenzylguanidine (MIBG)-(131)I or Na(131)I, the two most common forms of (131)I therapy. The results indicate that in 4 d following administration, the total excretion of volatile (131)I was 0.036 and 0.17 % of the administered activities of MIBG-(131)I and Na(131)I, respectively. As administered activities for (131)I therapy are typically of the order of 1-10 GBq, the overall excretion of volatile (131)I from a patient can be as high as 20 MBq. As a result, a family member can receive up to 0.07 mSv committed effective dose from inhaling the volatile (131)I excreted by the patient.

Excretion of volatile ¹³¹I from rats following administration of Na¹³¹I or MIBG-¹³¹I.

Epidemiological studies indicate long-term risks of ionizing radiation on the heart, even at moderate doses. In this study, we investigated the inflammatory, thrombotic and fibrotic late responses of the heart after low-dose irradiation (IR) with specific emphasize on the dose rate. Hypercholesterolemic ApoE-deficient mice were sacrificed 3 and 6 months after total body irradiation (TBI) with 0.025, 0.05, 0.1, 0.5 or 2 Gy at low (1 mGy/min) or high dose rate (150 mGy/min). The expression of inflammatory and thrombotic markers was quantified in frozen heart sections (CD31, E-selectin, thrombomodulin, ICAM-1, VCAM-1, collagen IV, Thy-1, and CD45) and in plasma samples (IL6, KC, MCP-1, TNFα, INFγ, IL-1β, TGFβ, INFγ, IL-10, sICAM-1, sE-selectin, sVCAM-1 and fibrinogen) by fluorescence analysis and ELISA. We found that even very low irradiation doses induced adaptive late responses, such as increases of capillary density and changes in collagen IV and Thy-1 levels indicating compensatory regulation. Slight decreases of ICAM-1 levels and reduction of Thy 1 expression at 0.025-0.5 Gy indicate anti-inflammatory effects, whereas at the highest dose (2 Gy) increased VCAM-1 levels on the endocardium may represent a switch to a pro-inflammatory response. Plasma samples partially confirmed this pattern, showing a decrease of proinflammatory markers (sVCAM, sICAM) at 0.025-2.0 Gy. In contrast, an enhancement of MCP-1, TNFα and fibrinogen at 0.05-2.0 Gy indicated a proinflammatory and prothrombotic systemic response. Multivariate analysis also revealed significant age-dependent increases (KC, MCP-1, fibrinogen) and decreases (sICAM, sVCAM, sE-selectin) of plasma markers. This paper represents local and systemic effects of low-dose irradiation, including also age- and dose rate-dependent responses in the ApoE-/- mouse model. These insights in the multiple inflammatory/thrombotic effects caused by low-dose irradiation might facilitate an individual evaluation and intervention of radiation related, long-term side effects but also give important implications for low dose anti-inflammatory radiotherapy.

Low-dose irradiation affects expression of inflammatory markers in the heart of ApoE -/- mice.

To assess health, growth and reproductive success of mammals exposed for multiple generations to levels of radium-226 known to occur in environments surrounding uranium mines and mills in Canada.

Michelle Bugden

Radiological Protection Research and Instrumentation

Canadian Nuclear Laboratories

Measuring DNA Damage and Repair in Mouse Splenocytes After Chronic In Vivo Exposure to Very Low Doses of Beta- and Gamma-Radiation