The study was concerned with a relationship between the influence of subcutaneously (s/c) transplanted LS and MMT1 tumors in a syngeneic system on the development of spontaneous and experimental lung metastases in mice and the dose of transplanted tumor cells. It was shown that the development of spontaneous of metastases in the lung depends on s/c transplanted tumor cells dose. Tumor inhibitory effect on experimental lung metastasis formation became apparent at doses ranging 10(6) -6 X 10(6), it rising proportionally to the increase in the dose of transplanted tumor cells. This relationship was more pronounced in MMT1 tumor-bearers. The relationship of experimental lung metastasis development and transplanted tumor cells was reproduced in the system of adoptive transfer of tumor-bearers' splenocytes to intact mice (no other splenocytes than those in mice with tumors induced by 2 X 10(6) of transplanted cells were capable of any antitumor activity). The blood serum of tumor-bearing mice blocked the antitumor effect of splenocytes.
The bone marrow, peripheral blood and spleen state was studied from the age aspect in Nude mice characterized by recessive nu mutation. A number of blood system peculiarities were revealed in homozygotic (nu/nu) mice by which they differed from the heterozygotic (nu/+) animals: low peripheral blood, bone marrow and spleen lymphocyte count, erythropoiesis depression in the bone marrow and erythroid element hyperplasia in the spleen.
The dynamics of population of alpha-fetoprotein (AFP)-containing cells in the liver and the level of AFP in the blood of C3H/HeJ+/+ and thymus-less mutant C3H/HeJnu/nu mice during postnatal development was studied by means of indirect immunofluorescence and radial immunodiffusion. The content of AFP-positive hepatocytes and AFP concentration in the blood serum of C3H/HeJnu/nu mice were shown to exceed markedly those in C3H/HeJ+/+ mice beginning from the age of 2 weeks. The histological analyses has revealed the foci of hemopoiesis in the liver of adult C3H/HeJnu/nu mice, unlike in the liver of normal mice. The neonatal thymectomy of C3H/HeJ+/+ mice did not influence the parameters under study. A possible relationship between the increased AFP level and the preservation of hemopoiesis in the liver of the mice homozygous by the mutation nude is discussed.
Results of the treatment of spontaneous pulmonary metastases by immunocorrection after tumour resection in mice and the analysis of antimetastatic activity of spleen macrophages (SM) by the method of adoptive transfer are presented. The injection of cytotoxic SM, NK-cells or the use of the biological response (lipid A and MDP-PE) modifiers cause no decrease in the number of lung metastases. The SM of operated mice, as distinct from the SM of immunocorrected mice causes the metastatic spreading in lungs of recipient mice. This effect is supposed to be mediated by the suppressor macrophages secreting prostaglandin E2 (PgE2). The treatment of mice with indometacin (inhibitor of the PgE2-synthesis) in the drinking water resulted in the 7-8-fold decrease in the number of lung metastases in operated mice.
The antimetastatic activity (AA) of spleen macrophages and T-lymphocytes of mice bearing four syngeneic tumours were tested in adoptive transfer system. Elimination of phagocytic cells by treatment with carrageenan or by carbonyl iron resulted in a complete (tumours LS, MMT1, MMT-T6I) or partial (MMT-T6I) AA decrease. Spleen macrophages (adherent cells) of tumour-bearers possessed a significant AA. The treatment of spleen cells both by anti-Thy-1-serum and by complement enhanced AA of spleen cells of LS and MMT1 tumour-bearers, but led to a partial AA suppression of spleen cells of MMT-T6I tumour-bearers. Thus, the efficiency of antimetastatic defence may considerably depend on the presence of synergism between macrophages and T-lymphocytes in realization of their AA.
The growth of the syngeneic tumor MMT1 in C3H of mice was accompanied by significant changes in the spleen weight and in the number of nucleated cells in the spleen. Tumor excision led to the reduction of these indicators to the initial level. Adoptive transfer of splenocytes from tumor-bearing to intact mice exerted an inhibitory (on days 5, 14) or stimulatory (on day 25) action on the development of experimental metastases in intact animals depending on the tumor growth time. The result of splenocyte transfer from the operated on mice depended on the presence or absence in donors of tumor growth relapses (the development of lung metastases was inhibited only by splenocytes from donors with tumor relapses). Splenocyte transfer from mutant nude mice, both tumor-bearing and intact, produced an equipotent inhibitory effect. It is suggested that different mechanisms may be responsible for the development of metastasis inhibition in normal tumor-bearing mice and in tumor-bearers with T-cell system immunity deficiency.
