Cellular events in radiation-induced lymphomagenesis.

Fractionated whole-body irradiation induces thymic lymphomas in most of treated C57Bl/Ka mice. The cellular events occurring during the latency period consist of the emergence of preleukaemic cells and of marked alterations to the T-cell lineage and the microenvironment within the thymus. The proportions of the various thymocyte subsets are modified, suggesting a blockage in the normal differentiation process. Thymic epithelial cells are functionally modified, leading to decreased interactions with immature thymocytes. Interestingly, bone marrow grafting early after irradiation, which inhibits the development of lymphomas, induces the disappearance of preleukaemic cells from the thymus, whereas thymocyte subpopulations and thymic epithelium are restored. Interferon gamma and tumor necrosis factor alpha also prevent the onset of lymphomas. Studies on the effect of bone marrow transplantation and cytokine inoculation in split-dose irradiated mice should allow characterization of the factors that modulate the progression of preleukaemic cells towards the neoplastic state.

Cellular aspects of the pathogenesis of radiation--induced thymic lymphomas in C57 BL mice (review).

Radiation-induced thymic lymphomas in C57Bl/Ka mice are interesting models for studying the successive steps of carcinogenesis. Irradiation initiates "preleukemic" cells, which are promoted to become neoplastic. Studies in mice in which lymphoma development is inhibited by a bone marrow transplantation after irradiation suggest that radiation--induced alterations to the T cell lineage, and particularly to thymic microenvironment, are critical for the promotion of preleukemic cells. It is proposed that the lack of physiological differentiation signals within the thymus, as a result of irradiation, allows these cells to escape the normal controls of thymocyte production and pushes them towards neoplastic transformation. A disturbance in the production of cytokines may be involved, since exogenous cytokines, such as Interferon gamma or Tumor Necrosis Factor a, can inhibit radiation-induced lymphomagenesis, reproducing the effects of bone marrow transplantation. The model is thus suitable for studying the mechanisms of carcinogenesis and designing biological manipulation devoted to cancer prevention in individuals who have been exposed to oncogenic agents.

Radiation leukemia virus: a marker for the study of intrathymic T cell differentiation.

Radiation Leukemia Virus (RadLV) is a retrovirus, which displays a highly specific thymotropism; after inoculation into young C57 BL/Ka mice, active virus replication is observed only in thymocytes and thymic lymphomas develop in most treated mice. The specific interaction between RadLV and the thymus resides in the particular susceptibility to infection of the most immature cells involved in the intrathymic lymphoid differentiation pathway and of non lymphoid thymic stromal cells. Recent data obtained from 'in situ' hybridization studies for detection of viral transcripts yield more detailed informations on these intriguing interactions.

Mammosomatotropes in human pituitary adenomas as revealed by electron microscopic double gold immunostaining method.

Hormone production was studied in situ by immunocytochemical methods in 20 pituitary adenomas. Special attention was given to 13 adenomas removed from acromegalic patients. Out of them, 6 had mild to moderate hyperprolactinemia. Immunohistochemistry revealed PRL-containing cells without any close relationship with high PRL serum level in 6 patients. Double immunogold staining revealed mammosomatotrope cells characterized by simultaneous presence of GH and PRL in the same granules in 2 patients. Since mammosomatotropes have never been demonstrated in the normal pituitary, our results probably signify gene dysregulation in pituitary cells of those acromegalic patients.

[Method of efficacious immunization against syngeneic murine sarcoma]. / Mise au point d'une procédure d'immunisation efficace contre un sarcome murin syngénique.

C57BL mice are immunized by subcutaneous injection of the T2 syngeneic tumour (MCA fibrosarcoma), followed a week later by surgical removal of the tumour. Such mice can be made hyper-immune by challenging them with mitomycin C-treated T2 cells and they do not develop a tumour after a subsequent inoculum of live T2 cells. Lymph nodes near the site of tumour inoculation are removed after 2 weeks and histological studies show an increase in the number of macrophages and mast cells but not of Lyt-2+ lymphocytes.

[Ultrastructural localization of pituitary hormones by immunocytochemical reactions in ultrathin sections of adenomas]. / Localisation ultrastructurale d'hormones hypophysaires par réaction immunocytochimique sur coupes fines d'adénomes.

Human pituitary adenomas were fixed in glutaraldehyde and embedded in epon. Ultrathin sections were incubated either with anti-hGH, anti-hPRL or anti-hLH. They were incubated with second step goat anti-rabbit immunoglobulins linked to gold particles. Two PRL secreting adenomas, one GH and PRL secreting adenoma, one ACTH secreting adenoma and two non secreting adenomas were studied. The specificity and the limits of the method were discussed in relation with the results obtained in light microscopy with the PAP method.

In vitro production of granular T cells and mast cells by use of different conditioned media. Ultrastructural and functional analysis.

Normal mouse spleen cells were cultured in different conditioned media (CM). Mixed lymphocyte culture supernatant (MLC SN) was shown to promote the proliferation of cytotoxic, Thy-1+, Lyt-1+, Lyt-2+, asialo-GM-1+, weakly adherent cells with numerous vacuoles and lysosome-like cytoplasmic granules. In contrast, the Con A SN induced the proliferation of non-cytotoxic, Thy-1-, Lyt-1-, Lyt-2-, asialo-GM-1-, non-adherent cells with numerous cytoplasmic granules. The ultrastructural morphology of these cells and the cytochemical characteristics of their granules enable us to identify them as mast cells. The different effects of both CM could be related to their T-cell growth factor (TCGF) content. When the amount of TCGF of these two CM was determined (by assaying growth-stimulating activity for T-cell colonies), it appeared that the MLC SN contained larger amounts of TCGF than the Con A SN used in these experiments.

Cytochemistry of mouse mast cell reaction to polylysine.

The modifications of mouse mast cells incubated in solutions of polylysine at two different concentrations are studied. At higher dose (0.5 mg/ml), the polycation has evident toxic effects. At lower dose (0.5 micrograms/ml), it induces some modifications of the granule morphology. Cytochemical reactions to demonstrate polyanions, basic proteins and organic bases are used to study the granule content. A polylysine treatment promotes the release of basic groups (vaso-amines) and sulphydryl-containing compounds (basic protein) from the mast cell granules. On the contrary, polyanions remain in the cells and correspond to the granule matrix persisting after amino-liberator treatment.

Ultrastructural autoradiographic study of blast cells in the mouse thymus. Interest for radioleukemia research.

Ultrastructural autoradiographic studies of mouse thymic blast cells after H3 Tdr injection show that their fine nuclear structure is related to their position in the cell cycle. The variations in the composition of the subcapsular blast cell population during radiation-induced leukemogenesis indicate kinetic changes in thymic lymphopoiesis, which are probably due to the oncogenic process.

[Influence of thymectomy on the lymphoid regeneration of hematopoietic bone marrow after sublethal irradiation]. / Influence de la thymectomie sur la régénération lymphoïde de la moelle hématopoïétique après une irradiation sublétale

In C57BL mice, bone marrow lymphoid regeneration after a sublethal irradiation is modified by a graft of normal marrow cells. This effect is suppressed in thymectomized mice since a lymphoid peak is observed after a 350 R irradiation; its composition is heterogeneous: small lymphocytes, lymphoblasts and peculier cells named "X cells". The same phenomenon is observed in mice where all the thymocytes and thymus derived and peripheral lymphocytes are destroyed. These results exclude that bone marrow lymphoid regeneration after irradiation is due to a migration of lymphoid cells of thymic origin to the marrow. They could be explained by the effect of a humoral thymic factor on marrow lymphopoiesis.