L. Fiore-Donati

INFLUENCE OF AGE ON SUSCEPTIBILITY TO LIVER CARCINOGENESIS AND SKIN INITIATING ACTION BY URETHANE IN SWISS MICE.

Influence of Age on Susceptibility to Liver Carcinogenesis and Skin Initiating Action by Urethane in Swiss Mice

Lung Carcinogenesis by Urethane in Newborn, Suckling, and Adult Swiss Mice

THERE is at present good evidence that urethane (ethyl carbamate) is a tumourinducing agent with a broad spectrum of activity. However, since the first observation of Nettleship and Henshaw (1943), lung seems to be the tissue most susceptible to the carcinogenic action of this chemical. In experiments previously reported (Fiore-Donati et al., 1961b) we observed that the administration of urethane to lactating mice gave rise to pulmonary adenomas in a high percentage of the offspring. A more extensive study, which is reported here, was designed to add new information on the influence of the age of animals and route of administration of urethane on lung carcinogenesis in mice.

Induction of malignant lymphomas by urethane in adult mice bearing syngeneic thymus grafts.

IN recent years it has repeatedly been proved that neonatal or very young animals are very susceptible to carcinogenesis induced by different agents. One possible explanation is that tissues of new-born animals contain a large number of incompletely differentiated cells, particularly responsive to carcinogenic stimuli. It is relevant to this speculation that a close correlation has been noted between susceptibility of mice to develop malignant lymphomas and the presence in the thymus of a great concentration of immature cells, whether by reason of early age1, genetic constitution2, whole-body X-irradiation3, or regenerative changes in implanted thymus4. In thymectomized, virus-inoculated5 or X-irradiated4 mice, implantation of new-born thymus proved much more effective than adult thymus in restoring leukaemogenesis.

Electron microscope study of the Graffi virus in the bone marrow of leukemic mice

Bone marrow from C57BL mice with myeloid leukemia induced by Graffi virus has been studied with the electron microscope by ultrathin section and negative stain techniques. Virus particles were usually found in different types of bone marrow cells as well as in extracellular spaces. However, the highest number of particles in various stages of maturation was observed in the cytoplasm of megakaryocytes. Two main types of virus particle were found: the immature Al particle and the mature C particle. They were morphologically indistinguishable from other murine leukemogenic viruses. In partially purified preparations studied by negative staining, some of the particles which were not penetrated by PTA, frequently showed a tail-like structure of variable length. In ultrathin sections, particles were found to originate by budding from the cell membranes. Budding of particles was particularly evident in megakaryocytes and especially within the granules and cytoplasmic vesicles or in connection with the platelet demarcating membranes. The findings of a high number of virus particles in all stages of maturation in megakaryocytes together with a certain degree of megakaryocytosis observed in the bone marrow suggest that this type of cell is possibly one of the main source of production of the virus. A few particles resembling morphologically mycoplasma were detected within the cytoplasm of some immature bone marrow cells.

Lymphocyte interactions in the presence of mitogens. New possibilities of exploring histocompatibility in the mouse and man.

SUMMARY An in vitro assay for exploring histocompatibility, which gives linear and reproducible results in 48 hr, has been obtained by briefly incubating the target cells with phytohemagglutinin (PHA) and mixing them with increasing amounts of allogeneic untreated cells. The effect of incompatibility is detectable as the percentage of inhibition of PHA response of the target and is sensitive enough to detect H-2 and non-H-2 differences from unprimed and sensitized cells. The assay is applicable to human lymphocyte cultures.