EUROPEAN RADIATION RESEARCH 2012

Effect of Internal Contamination with HTO on the Innate Anti-Tumour and Inflammatory Reactions in Mice

17 Oct 2012, 16:43

1m

Poster Hall (Vietri sul Mare)

poster preferred Internal Emitters Poster Session 2

Speaker

Dr Ewa M. Nowosielska (Military Institute of Hygiene and Epidemiology)

Description

One of the significant sources of internal radiation exposure of workers and members of the public is tritium, a β--emitting isotope of hydrogen that binds with hydroxyl radicals to form the easily internalized tritiated water (HTO). As with other exposures to low-LET ionizing radiation deposition of HTO in the body leads to absorption of energy in the sensitive targets which, in the long run, can apparently instigate or promote tumour development. Thus, we aim in the present project granted by the Polish National Science Centre is to estimate whether internal contamination of mice with HTO modifies the development of pulmonary tumour metastases and whether this effect can be associated with alterations in the anti- or pro-neoplastic functions of macrophages and NK lymphocytes. The studies will be carried out on two strains of mice (BALB/c and C57BL/6) that differ in their sensitivity to ionizing radiation and whose pro-inflammatory and macrophage-type responses are differently expressed. Mice will be intraperitoneally injected with HTO at such activities that the total absorbed doses of radiation delivered to a mouse will be 0.01, 0.1 or 1.0 Gy; control mice will be injected with PBS. Starting on day 7 post-injection the following parameters will be assessed: cytotoxic activity of NK cells, nitric oxide production by macrophages (as a marker of the cytolytic function of these cells against susceptible tumour targets), spleen and bone marrow cellularity, leukocyte and thrombocyte counts in peripheral blood, serum levels of selected pro- and anti-inflammatory cytokines, and development of the induced tumour nodules in the lungs. Thus far, we have conducted only preliminary studies using BALB/c and C57BL/6 mice i.p. injected with HTO at total absorbed doses of 0.01 Gy (a dose encountered in some occupational settings) and 0.1 (upper limit of the low-dose region) only to find that peritoneal macrophages obtained from the two strains produced elevated amounts of NO, but in the BALB/c macrophages this effect was pronounced after internal contamination with HTO at 0.1 Gy, whereas in the C57BL/6 macrophages after contamination at 0.01 Gy. The obtained results will broaden our understanding of bio-medical outcomes of internal contamination with tritium by furnishing evidence of its anticipated pro- or anti-neoplastic and/or pro- or anti-inflammatory effects.