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Mice treated with strontium 90: an animal model deficient in NK cells
Abstract:
Treatment of BALB/c mice with radioactive isotopes of the bone-seeking element strontium reduces the percentage of specific NK-cell cytotoxicity to only 2.6%, compared with 13.6% for normal BALB/c and 36.3% for athymic (nude) BALB/c. The syngeneic plasmacytoma NS-1 was used as target in a 4th in vitro NK-cell microassay. Marrow cellularity in treated mice is reduced to 12.5% of controls, but haemopoietic and stem-cell functions are taken over by the spleen and the peripheral blood picture remains relatively normal. Allogenic (H-2k) tumour transplants are rejected normally with good anti-H-2k alloantibody response. Haemopoietic and T- and B-cell functions are therefore substantially intact, and the defect seems confined to NK cells. In vivo, after s.c. inoculation of 10(6) NS-1 cells, 8/12 controls grew a solid tumour after a mean delay of 30.5 +/- 1.25 (s.e.) days, whereas 5/6 90Sr-treated mice grew the tumours after a delay of only 10.5 +/- 1.8 days. This markedly reduced delay in the 90Sr-treated mice lends support to suggestions that NK cells play an important role in resisting the establishment of tumour foci (i.e. in antitumour surveillance). Mice treated with 90Sr could be useful in evaluating the in vitro role of NK cells.
Insights
Strontium-90 (90Sr) treatment significantly impairs natural killer (NK) cell activity in mice, reducing their ability to control tumor growth. This highlights the critical role of NK cells in anti-tumor surveillance and suggests 90Sr-treated mice are valuable models for studying NK cell function.
Area of Science:
- Immunology
- Radiobiology
- Cancer Research
Background:
- Natural killer (NK) cells are crucial for innate immunity and tumor surveillance.
- Radioactive isotopes like Strontium-90 (90Sr) can affect immune cell populations.
- Understanding the specific impact of 90Sr on NK cell function is important for both radiobiology and cancer research.
Purpose of the Study:
- To investigate the effect of 90Sr treatment on NK cell cytotoxicity and anti-tumor responses in BALB/c mice.
- To determine if the observed immune defects are specific to NK cells or affect other immune components.
- To evaluate the utility of 90Sr-treated mice as a model for studying NK cell-mediated tumor resistance.
Main Methods:
- BALB/c mice were treated with 90Sr, a bone-seeking radioactive isotope.
- NK cell cytotoxicity was assessed in vitro using a microassay with the syngeneic plasmacytoma NS-1 as target cells.
- Tumorigenicity and rejection of allogeneic tumor transplants were evaluated in vivo following subcutaneous inoculation of tumor cells.
Main Results:
- 90Sr treatment drastically reduced NK cell cytotoxicity to 2.6% compared to controls (13.6%).
- Marrow cellularity decreased significantly, but spleen compensated for hematopoietic functions, maintaining relatively normal peripheral blood counts.
- While T- and B-cell functions remained intact, 90Sr-treated mice showed a markedly reduced delay in tumor growth, indicating impaired anti-tumor surveillance.
Conclusions:
- NK cells play a significant role in resisting tumor establishment, as evidenced by the impaired tumor control in 90Sr-treated mice.
- The immune defect induced by 90Sr appears largely confined to NK cells, sparing other hematopoietic and lymphoid functions.
- Mice treated with 90Sr serve as a valuable preclinical model for in vitro and in vivo studies of NK cell function in tumor immunity.