Temporal Changes in Cell Populations of Mice Lymphoid Organs after Single Injection of Carcinogenic Urethane

Abstract

The development of urethane-induced lung tumors is preceded by circaseptan rhythm disturbances both in the target organ and in the lymphoid organs. (Ryabykh et al., 1994). Time series analysis was performed to elucidate which cell population(s) contributes to the rhythm disturbances in the cellularity of the lymphoid organs of mice during urethane carcinogenesis. Three times a week during a 2-month period cellularity and cellular composition of thymus, lymph nodes and spleen were examined both in control mice and in experimental group mice. Monoclonal antibodies Thy-1, Lyt-2, L3/T4 and IgM were used for flow cytometric analysis of lymphocytes. Functional activity of the non-lymphoid cells was evaluated by luminol-amplified chemiluminescence. Time series were analysed by the cosinor method and with Statgrafics statistical software. Rhythms with periods from about 7 days to about 20 days were demonstrated both in the control and in the experimental group. After single carcinogenic injection significant temporal changes in organ cellularity were found as compared to controls. The change in spleen cellularity was negatively correlated with the proportion of T (Thy-1) cells (r = –0.812, p<0.01), did not correlate with the proportion of B (IgM) cells and was positively correlated with the percentage of non-lymphoid cells (r = 0.675, p<0.01). A positive correlation was also found between the variation in cellularity and the variation in spontaneous and phagocytosis-stimulated chemiluminescence of splenic cells. Phagocytic cells (“inflammatory cells”) might account for these changes. Changes in cellularity of the thymus (from –35% to +70%) and the lymph nodes (from –60% to +40%) as compared to controls were due to changes in the number of Thy-1 cells. The change in cellularity of the lymph nodes was negatively correlated with the change in percentage of Lyt-2 cells (killers+suppressors). The data obtained testify that inflammatory cells may play an important role in urethane-induced carcinogenesis.