Abstract
Tritium is a potentially significant source of internal radiation exposure which, at high levels, can be carcinogenic. We evaluated whether single intraperitoneal injection of BALB/c and C57BL/6 mice with tritiated water (HTO) leading to exposure to low (0.01 or 0.1 Gy) and intermediate (1.0 Gy) cumulative whole-body doses of β radiation is immunosuppressive, as judged by enhancement of artificial tumour metastases, functioning of NK lymphocytes and macrophages, circulating cytokine’s levels, and numbers of bone marrow, spleen, and peripheral blood cells. We demonstrate that internal contamination of radiosensitive BALB/c and radioresistant C57BL/6 mice with HTO at all the absorbed doses tested did not affect the development of neoplastic colonies in the lungs caused by intravenous injection of syngeneic cancer cells. However, internal exposure of BALB/c and C57BL/6 mice to 0.1 and 0.01 Gy of β radiation, respectively, up-regulated cytotoxic activity of and IFN-γ synthesis in NK lymphocytes and boosted macrophage secretion of nitric oxide. Internal contamination with HTO did not affect the serum levels of pro- (IL-1β, IL-2, IL-6, TNF-α,) and anti-inflammatory (IL-1Ra, IL-4, IL-10) cytokines. In addition, exposure of mice of both strains to low and intermediate doses from the tritium-emitted β-particles did not result in any significant changes in the numbers of bone marrow, spleen, and peripheral blood cells. Overall, our data indicate that internal tritium contamination of both radiosensitive and radioresistant mice leading to low and intermediate absorbed β-radiation doses is not immunosuppressive but may enhance some but not all components of anticancer immunity.
Highlights
In contrast to the well-characterized effects of external radiation exposures, biological effects of internal contamination with radioisotopes are not as well characterized and understood, especially for low and intermediate cumulative radiation doses
In two preliminary experiments conducted on BALB/c and C57BL/6 mice exposed to 0.1 Gy of radiation, no significant differences in the cytotoxic activity of the natural killer (NK) cellenriched splenocytes were detected between the control and irradiated groups beyond days 14–16
Cytometric analysis of the anti-mouse CD335 (NKp46)-labelled splenic NK cells obtained from contaminated BALB/c and C57BL/6 mice showed that for each absorbed dose studied, there was no significant increase in the percentages of these cells; this effect was comparable in the two strains of mice and was detectable both before and after the splenocyte suspension was purified on the nylon wool columns (Table 1)
Summary
In contrast to the well-characterized effects of external radiation exposures, biological effects of internal contamination with radioisotopes are not as well characterized and understood, especially for low and intermediate cumulative radiation doses. It was recommended that a review be conducted of the relevant risk of internal radioisotope exposures (COMARE 2004). One of the significant sources of internal radiation exposure of workers and members of the public is tritium (3H), a β-emitting isotope of hydrogen with low-to-intermediate values of linear energy transfer (LET). According to the suggestion by the Canadian delegation to United Nations Scientific Committee on the Effects of Atomic Radiation (UNSCEAR 2010), potential adverse biological effects of tritium should be of special interest because there is evidence that its relative biological effectiveness (RBE) factor may be as high as two or more
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