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The rates of spontaneous metastasis to the lung (SML) and lymph nodes, cytotoxic and antimetastatic activity (AA) of macrophages in the course of and after resection of transplantable mammary adenocarcinoma MMTI as well as cloned tumor MMTv4 were studied in C3Hf mice. Murine macrophages showed AA in adoptive test in the course of MMTv4 growth and specific cytotoxic activity in tests in vitro. Macrophages from bearers of MMTv4 revealed non-specific cytotoxicity only. After tumor resection, a sharp increase in SML and metastasizing into lymph nodes was matched by a lack of AA and cytotoxic activity on the part of macrophages in mice operated on. In tumor cell recipients, they were found to stimulate metastasis formation. Only 60% of operated mice survived and macrophages obtained from them did not reveal any metastasis-stimulating activity. This activity was further curbed due to injections of indomethacin--an inhibitor of prostaglandin E2 synthesis--or as a result of indomethacin pretreatment of macrophages in vitro. The above data implicate suppressor activity in the explosion of metastatic formation observed after tumor resection. The role of macrophage suppressors and that of of prostaglandin E2 in postsurgical stimulation of metastasis spreading are 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.

Activation of extramedullar hemopoiesis in the liver together with an appreciable elevation of the alpha-fetoprotein (alpha-FP) level in the blood were observed in CBA, C3H/HeJ, DD, C57BL/6 and CC57BR/Mv mice after a single injection of cyclophosphane in a dose of 200 mg/kg bw. The alpha-FP concentration reached maximum days 2-4 after cyclophosphane administration, amounting of 290-560 ng/ml which surpasses 2-5-fold the basal level of the protein. In mice with an earlier serum alpha-FP elevation (CBA, C3H/HeJ and DD), the liver hemopoiesis also started earlier than in those with a delayed alpha-FP maximum (C57BL/6 and CC57BR/Mv).

The influence of transplantable MMTI and LS strain tumors on lung metastasis development was studied. Tumors were induced by subcutaneous injection of tumor cells. It was shown that MMTI and LS subcutaneous tumors inhibit the process of lung metastasis development at different rates: the inhibitory effect of MMTI tumor was higher than that of LS tumor. The inhibitory effect was not tumorspecific. There was no correlation between tumor size and the degree of the inhibitory effect.

Cells of lines of mice transplantable tumours metastasizing into the lung have been used: lung adenocarcinoma (AL), Lewis lung carcinoma (LL), melanoma B-16 (B-16), mammary tumour MMT-1 (MMT-1), malignant subline of L-cells (LS). Hybrid vesicles were obtained for each tumour. They contain fragments of cell plasmatic membranes (PM). It has been shown that AL-, LL-, LS- and B-16-liposomes were accumulated in lung, the trapping of AL- and LL-liposomes being higher than that of the other hybrid vesicles. Despite the similar dynamics and frequency of metastatic spreading into the lung for all tumours studied, no trapping of MMT-1-vesicles in the target-organ was observed. The role of specific interaction of tumour cells PM with the endothelium of the lung capillaries in the process of organotropic metastatic spreading is discussed.

Hemopoietic cells at different stages of differentiation were found in the liver imprints of adult thymus-less mutant mice BALB/c nu/nu, thus suggesting the presence of extramedullary hemopoiesis. During the postnatal development the intensity of leucopoiesis in the liver of mutant animals increased reliably and that of erythropoiesis suffered no marked changes. In the liver of adult BALB/c nu/nu mice, a high content of stem hemopoietic cells was found. The subcutaneous implantation of thymus to 2 weeks old BALB/c nu/nu mice resulted in the reliable decrease of leuco- and erythropoiesis in the liver. The neonatal thymectomy of the control mice BALB/c+/+ did not prevent the switching embryonic hemopoiesis in the liver off. A question of regulating influence of thymus on the process of switching hemopoiesis in the mouse liver off is discussed.

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.

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 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.

The role of macrophages in the development of the inhibitory effect of subcutaneously transplanted tumor on the formation of experimental metastases in the lung was studied. Four murine lines of tumor were investigated in a syngeneic system. The treatment of tumor-bearing mice with antimacrophage agents (carrageenan or silica) proved to stimulate experimental metastasis formation which correlated with the absence of antitumor activity of splenocytes tested in a transfer system (by counting lung metastases). Antitumor activity of the following types of splenocytes of tumor bearers was studied in this system: intact, those treated in vitro with different doses of carrageenan, separated from macrophages by carbon iron and, vice versa, enriched with macrophages. It was shown that (I) antitumor activity of tumor-bearers' splenocytes correlates with the ability of relevant tumors to inhibit experimental lung metastasis formation, (2) the key role in this effect is played by activated macrophages of the spleen, and (3) activation of macrophages is not tumor-specific.

A comparative analysis of metastatic spread into lungs after tumor removal in immunologically normal mice (group 1) and those with splenectomy, thymectomy and congenital athymia-induced immunity disorders (group 2) was conducted. The largest number of lung metastases was found after tumor removal in group 1, the smallest in nude mice (group 2). The use of any method of lowering T-lymphocyte level (splenectomy, thymectomy or a single administration of low-dose cyclophosphamide) was shown to result in a significantly smaller number of lung metastases after tumor removal. It is suggested that formation of metastases after tumor removal is caused by an immunological factor which is possibly associated with an active response of T-suppressors.

The paper is concerned with the effect of thymosin, a hormone secreted by the thymus (fraction 5), on the development of adrenocortical and sex gland functions in genetically athymic mice (nude mutation). Multiple administration of thymosin to mice in the 1st month of their life (0.1 microgram/mouse twice a week) caused the suppression of corticosterone production by the adrenal glands in adult mice aged 2 mos., a considerable rise of the blood level of testosterone in male mice and the reduction of the specific production of estradiol by the ovaries in females. A thymosin-mediated role in the interaction between the immune and endocrine systems in the period of development of their functions was discussed.

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.