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Published on: September 19, 2013
[Determination of target cells in the by N-nitroso-N-methylurea induced leukemogenesis in the mouse]
Abstract:
Using the model of chemically induced leukemogenesis of mice by N-nitroso-N-methyl urea (NMU) studies were done to find out the primary point of attack of the chosen carcinogen on cellular level. After application of 14C-NMU (XVII X AKR) F1 hybrid mice were killed at different times, and the 14C activity was determined in various organs by scintillation counting and autoradiography. Contrary to expectations, the bone marrow showed a significantly higher activity than the thymus, which is supposed to be the target organ for lymphatic leukemogenesis. The specificity of the enrichment of 14C activity in bone marrow could be assured by comparative proliferation studies. The autoradiographic results favor the lymphatic cells of bone marrow as target for NMU. The target cell problem is discussed in respect to thymectomy and recent results on nude mice. With high probability the thymus is not essential for lymphatic leukemogenesis and, consequently, is not the target organ.
Insights
N-nitroso-N-methyl urea (NMU) primarily targets bone marrow, not the thymus, in chemically induced leukemogenesis. This finding challenges the traditional view of the thymus as the main target organ for lymphatic leukemia development.
Area of Science:
- Oncology
- Toxicology
- Cell Biology
Context:
- Chemically induced leukemogenesis models are crucial for understanding leukemia development.
- N-nitroso-N-methyl urea (NMU) is a known carcinogen used to induce leukemia in mice.
- The thymus has been historically considered the primary target organ for lymphatic leukemogenesis.
Purpose:
- To identify the primary cellular target of N-nitroso-N-methyl urea (NMU) in chemically induced leukemogenesis.
- To investigate the distribution and accumulation of 14C-labeled NMU in various organs of mice.
- To clarify the role of the thymus versus bone marrow in NMU-induced lymphatic leukemogenesis.
Summary:
- Studies using 14C-NMU in (XVII x AKR) F1 hybrid mice revealed significantly higher NMU activity in bone marrow compared to the thymus.
- Autoradiography and scintillation counting confirmed bone marrow as the primary site of NMU accumulation.
- Autoradiographic evidence suggests lymphatic cells within the bone marrow are the likely target cells for NMU's leukemogenic effects.
Impact:
- Challenges the established understanding of the thymus as the essential target organ for lymphatic leukemogenesis.
- Provides evidence that bone marrow, specifically its lymphatic cells, is the critical target for NMU-induced leukemia.
- Suggests thymectomy may not be essential for preventing lymphatic leukemogenesis, re-evaluating therapeutic strategies.
