Effect of internal contamination with tritiated water on the neoplastic colonies in the lungs, innate anti-tumour reactions, cytokine profile, and haematopoietic system in radioresistant and radiosensitive mice

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.

A 3D In Vitro Model of the Human Airway Epithelium Exposed to Tritiated Water: Dosimetric Estimate and Cytotoxic Effects

“…Intraperitoneal injection of HTO is also used to mimic internal contamination by tritium, though in a single exposure. Nowosielska et al (30) demonstrated that doses between 0.01 and 0.1 Gy do not lead to immunosuppression (evaluating the possible enhancement of artificial lung tumor metastases) and do not affect the serum levels of pro-and anti-inflammatory cytokines, but may enhance some components of anticancer immunity.…”

Transcriptome Analysis of the Immortal Human Keratinocyte HaCaT Cell Line Damaged by Tritiated Water

“…Some previous reports in the literature proved that tritiated water could also inhibit the vitality of Human Umbilical Vein Endothelial Cells and cause cell senescence after long–term exposure [ 13 , 14 , 15 ]. In addition, tritiated water could also affect the vitality of rat lymphocytes and NK cells in terms of the immune system [ 16 , 17 ]. As a radioactive element, the damage to cells of tritiated water mainly included the following two aspects: first, tritium β –decay released energy, resulting in DNA single-strand break (SSB) or double-strand break (DSB), leading to cell apoptosis or cell senescence [ 34 , 35 ].…”

“…Balonov et al found that exposure to tritiated water in rats for 6 months at 3.7 × 10 4 Bq·g −1 /Kg induced skin cancer and osteosarcoma [ 12 ]. In addition, tritium radiation damaged the cardiovascular [ 13 , 14 , 15 ], immune [ 16 , 17 ] and reproductive [ 18 ] systems. Li et al found that when human B lymphocytes (AHH-1-1) were treated with 3.7 × 10 9 Bq/L tritiated water for 48 h, cell apoptosis could be observed [ 17 ].…”

“…Lee et al proved that micronucleus appeared in the blood samples of rats exposed to tritiated water after 14 d in rats with a total oral dose of 3.7 × 10 4 Bq, and the appearance of micronucleus, which represents chromosome aberration. Nowosielska et al treated mice with tritiated water of 0.888, 8.88 or 88.8 × 10 12 Bq, and found that after 8 d, NK lymphocytes were damaged and that tritiated water promoted increased NO by macrophages [ 16 ]. Kamiguchi et al found that after treating human sperm with 5.66–59.91 × 10 5 Bq/mL tritiated water for 80 min, the incidence of chromosome aberration in the sperm structure increased linearly in a dose-dependent manner [ 18 ].…”

Radiobiology of Select Radionuclides in Hanford Site Tank Waste

“…Recent research suggested that low doses of tritium may in fact stimulate the immune system, potentially resulting in a decrease in the risk (Wang et al 2019). With care, tritium in nuclear workers has been limited to levels that are well below established standards and in the range of natural background (Nowosielska et al 2018). If the tritium is incorporated into DNA or proteins, it clears more slowly, can result in transmutational effects (Oliphant et al 1934), and has a higher effectiveness factor (about 2).…”