[Diethylstilbestrol-induced uterine sarcoma in mice]. / Sarkomy matki myshei, indutsirovannye diétilstil'béstrolom.

Female mice of CBA strain received diethylstilbestrol (DES) 1 g body weight intraperitoneally. High incidence of histiocytic uterine sarcoma was observed in parents (25%), first generation (F1), descendants (10.9%), and generation F2m (through F1 males mated with females in control) (17.8%). Morphologically, tumor cells examined through light and electron microscopy were referred to as histiocyte-like elements. Half of the animals had metastases in the liver, kidneys, lungs, spleen, pineal and adrenal glands and stomach. The development of tumors in generation F2m, which was not exposed to DES, might be accounted for by "transgeneration" carcinogenesis, i.e. passage of carcinogenic effect through a generation.

[N-nitrosodiethylamine-induced changes in the liver of syrian hamster with superinvasive opistorchiasis]. / Izmeneniia v pecheni khomiachkov, indutsirovannye n-nitrozodiétilaminom pri superinvasionnom opistorkhoze.

Trematoda O. felinius-induced hepatic lesions were investigated in Syrian golden hamsters with superinvasive opistorchiasis. One hundred hamsters were divided into 4 groups: (1)--control; (2) N-nitrosodiethylamine (DENA), i.p., twice a week, 3 weeks, total dose 72 mg/kg; (3) metacercariae O. felinius, with drinking water, 3 injections per day, once in 2 weeks, and (4) metacercariae O. felinius, as in group 3, followed by DENA, as in group 2. Animals were sacrificed 12 months after the beginning of the study. No changes in the liver were found in group 2. Reddish protrusions, up to 4 cm in diameter, appeared on liver surfaces in groups 3 and 4. Group 4 featured the highest relative and absolute weights of liver as well as clusters of oval cells and cholangiocellular tubules and cholangiofibrosis (in group 3, they were less visible). Electron microscopic examination identified hepatocytes with destructive changes to plasmalemma, nucleus and cytoplasmic organelles. Also, perisinusoidal cells (Ito cells) occurred. Tumor-bearing animals showed low hepatic cytochrome P-450. It is suggested that proliferative growth in the liver was stimulated by opistorchis invasion.

Comparative study of lipid composition and proliferative activity of rat cholangiocarcinoma RS1 and sarcoma M1 depending on the transplantation organ.

The proliferative activity and lipid composition (phospholipids, gangliosides) were studied in rat cholangiocarcinoma RS1 and sarcoma M1 transplanted subcutaneously or intrahepatically. The mitotic index was higher in the tumors transplanted into the heterologous organ. The total phospholipid and sphingomyelin contents were higher in the tumors transplanted intrahepatically. GM3 and GD3 were the main gangliosides in both variants of each tumor. A significant amount of GM3 ganglioside lactone was found in the intrahepatic variants whereas it was absent in the subcutaneous tumors. Both the mitotic index and lipid composition of the tumors studied depended on their microenvironment.

Differences in lipid composition and proliferative activity of rat hepatoma-27 depending on the target organ.

Proliferative activity and lipid composition (phospholipids and gangliosides) were studied in rat hepatoma-27 transplanted subcutaneously or intrahepatically (as models for primary and metastasizing tumors). The mitotic index of subcutaneously transplanted hepatoma far exceeded that of the intrahepatically transplanted tumor. The overall amounts of both phospholipids and gangliosides increased appreciably in the subcutaneously growing hepatoma (in contrast to the intrahepatically growing tumor) in comparison to the control hepatic tissue. The ganglioside composition in the tumors differs from that in the liver: ganglioside GD3 appears, whereas gangliosides GD1b and GT1b decrease in amount in the intrahepatic tumor compared to the control liver and disappear in the subcutaneously transplanted hepatoma. In both tumor types, the amounts of both phosphatidylethanolamine and sphingomyelin exceed the control values. Comparison of these results with previously reported data concerning the phospholipid and ganglioside composition in the regenerating rat liver indicates that the difference in the lipid composition between the subcutaneously and intrahepatically growing hepatomas-27 is due to their different proliferative status and also their microenvironment.

Different pathways for mitogenic and enzyme induction signal transduction by cytochrome P450 inducers.

The correlation between enzyme induction and cell proliferation caused by inducers of xenobiotic metabolizing enzymes was studied using a cell culture expressing a constitutive level of cytochrome P450 (hepatoma McA RH 7777) and a cell culture in which cytochrome P450 was absent (hepatoma 27). In hepatoma 27 cells, the inducers did not induce the synthesis of xenobiotic metabolizing enzymes but stimulated cell proliferation. Thus, the processes of signal transduction for enzyme induction and for cell proliferation by the inducers are different.

Renal cell tumours in mice: electron microscopy versus immunohistochemistry.

15 renal cell tumours induced in CBA male mice by 1,2-dimethylhydrazine were studied electronmicroscopically (EM). All these tumours earlier were investigated histochemically and immunohistochemically with the use of gamma-glutamyltranspeptidase (GGT) as a marker of the proximal tubules and antigen A6 as a marker of distal tubules and/or collecting ducts. One of the tumours was GGT-positive and antigen A6-negative and ultrastructurally well developed brush border was found. This correlation between immunohistochemistry and EM data allowed to conclude that the site of origin of this tumour were the cells of the proximal tubules. All other tumours were GGT-negative and antigen A6-positive, i.e. the development of these tumours from the distal tubules (and not from the proximal tubules) could be suspected. However in 5 of these neoplasms reduced brush border was found. Microvilli were of a smaller size than in normal proximal tubules and were frequently located not on the apical cell surface but in the narrow spaces between two cells. Invaginations and apical vesicles typical for the normal proximal tubules were also found in some tumour cells. EM and immunohistochemical data combined allow to suggest the origin of these tumours from the common precursor cell capable of differentiation, in the course of tumour progression, into the cells with properties of proximal and/or distal tubules.

[Xenograft of human RShM32 cervical cancer and comparative DNA flow cytometry]. / Geterotransplantat raka sheiki matki cheloveka RShM 32 i sravnitel'naia tsitometriia DNK.

Xenograft CC-32 was obtained from uterine cervical carcinoma of 24 years old woman in IV stage of the disease. Morphological diagnosis of clinical material and xenograft at various passages was the same-squamous cell carcinoma. Examination tumour DNA showed HPV-16 DNA integrated in five selected points. Tumor CC-32 contained a large quantity a diploid and tetraploid cells in contrast with another cervical carcinoma xenograft.

[Mouse hepatoblastoma: comparative aspects]. / Gepatoblastoma myshei v sravnitel'nom aspekte.

The structure of 12 spontaneous hepatoblastomas found in old (average age 26.5 months) male mice is described. There were considerable strain differences in their incidence: 0.5% (1/194), 0.5% (1/194) and 5% (10/198) in strain C57B1, CBA and F1 (CBA X C57B1), respectively. This proves the importance of genetic factor the role of which in the development of human hepatoblastoma is not established so far. Mouse hepatoblastoma develops almost invariably within or adjacent to liver cell tumours (adenoma or carcinoma). There was a correlation between the incidence of liver cell tumours within a given strain treated with different doses of carcinogen but such correlation was absent in mice of different strains. Histologically and ultrastructurally, mouse hepatoblastoma corresponds to the anaplastic variant of human hepatoblastoma. As distinct from human tumour, mouse hepatoblastoma does not contain alpha-fetoprotein. One tumour was transplanted to the syngeneic host and passed 30 transplant generations retaining the structure of a primary tumour with areas of osteoid tissue and foci of squamous cell metaplasia. Mouse hepatoblastoma may be induced by carcinogens. Likewise, according to the literature, risk of hepatoblastoma is higher in children whose mothers were exposed to the potential carcinogens before or during the pregnancy.

[The ultrastructural localization of antigen B10 of the hepatocyte plasma membrane in mouse hepatomas]. / Ul'trastrukturnaia lokalizatsiia antigena B10 plazmaticheskoi membrany gepatotsita v gepatomakh myshi.

The ultrastructure of the murine hepatocyte plasma membrane antigen (Ag B10) was studied by immunoelectron microscopy in 5 spontaneous and 3 chemical-induced hepatomas. Ag B10 was associated with plasmalemma of bile canaliculi and membrane of microvilli as in normal liver. Sometimes it was connected with plasmalemma of lateral domain of tumor cells. The availability of Ag B10 in the matrix of bile canaliculi and within microvilli was shown.

Transplantable mouse hepatoblastoma: histologic, ultrastructural and immunohistochemical study.

Hepatoblastoma found adjacent to a liver cell adenoma in an aged (CBA x C57Bl/6)F1 male mouse was transplanted to the syngeneic host and passed through 30 generations. Histologically, tumours that grew on transplantation retained principal morphological features of the primary tumour. Transplanted tumours were negative for AFP and for antigen A6. This antigen in the normal mouse liver is found in epithelial cells lining bile ducts and ductules including the terminal Hering canals. Some of the Hering cells were consistently A6 negative under normal conditions, and the suggestion is made that these A6 negative cells might be the cells of hepatoblastoma origin.

[Electron microscopic detection of the proteoglycan component of the extracellular matrix in osteogenic sarcomas]. / Elektronno-mikroskopicheskoe vyiavlenie proteoglikanovogo komponenta vnekletochnogo matriksa osteogennykh sarkom.

Electron-microscopic studies in which Alcian blue was used to demonstrate proteoglycans (PG) revealed a predominance of largely undifferentiated tumor cells in two of the osteosarcomas examined; the extracellular matrix of these tumors had few PG-containing structures. Other osteosarcomas, where cells of the osteoblastic type prevailed, were found to possess PG granules on the cell surface and a rough PG network in the pericellular space. In a parosteal osteosarcoma, which contained strongly elongated fibroblast-like cells, PG formed a fine mesh both in the pericellular space and throughout the extracellular matrix. A correlation therefore exists between the ultrastructure of the PG component in the extracellular matrix of osteogenic sarcomas and the degree and direction of tumor cell differentiation.

[Effect of an opioid peptide on the healing of experimental myocardial infarct]. / Vliianie opioidnogo peptida na zazhivlenie éksperimental'nogo infarkta miokarda.

The effect of an opioid hormone (Leu-enkephalin analog Tyr-Dala-Gly-Phe-Leu-Arg) on the healing of myocardial infarction caused by the ligation of the descending branch of the rabbit left coronary artery has been investigated. The peptide was injected intraperitoneally at a dose of 10 micrograms/kg daily. Using light and electron microscopy, the peptide has been shown to exert a pronounced stimulating effect on the healing of the necrotic zone on days 3 and 7 of the experiment. Opioid peptides are suggested to take part in the healing of various disorders.

[Ultrastructure of the proteoglycan component of the extracellular matrix in the intact mammary gland and in benign and malignant mammary gland tumors]. / Ul'trastruktura proteoglikanovogo komponenta vnekletochnogo matriksa v intaktnoi molochnoi zheleze, a takzhe v ee dobrokachestvennykh i rakovykh opukholiakh.

Proteoglycans (PG) were revealed by electron microscopy using cation dyes, Alcian blue and safranin O. In intact mammary gland of dogs, each histogenetic type of cells had its specific features in the ultrastructure of pericellular matrix proteoglycan component. A thin-stitched net, consisting of small PG granules and thin filaments has been observed in the pericellular space of secretory epithelium. A well-proportioned PG net is absent near fibroblasts and macrophages. Net-like PG structure is found in the endothelium, pericytes and adventitial cells of blood capillaries. Visual changes in PG-containing extracellular matrix are observed in the epithelium of mammary gland tumors.

[Localization of different types of collagen (I, III, IV, V) in the connective tissue of the popliteal artery and skeletal muscle of man (immunoelectronmicroscopic analysis)]. / Lokalizatsiia razlichnykh tipov kollagena (I, III, IV, V) v soedinitel'noi tkani podkolennoi arterii i skeletnoi myshtsy cheloveka (immunoélektronno-mikroskopicheskii analiz).

By means of immunoperoxidase and immunoferritin techniques collagen of the I, III, IV and V types has been revealed in cryostat sections of the popliteal artery and in the musculus quadriceps of the femur. Areas of the vascular wall without any macroscopical signs of lesions have been investigated. They have been obtained from amputated extremities of young persons (17-22 years old), and muscle pieces have been taken during operations performed in the knee joint. After certain immunocytochemical procedures the cryostat slices are embedded in mixture of epon 812 and araldit, non-contrasted ultrathin slices are examined in the electron microscope JEM 100CX. Collagen of the I and III types is revealed in fibrills 20-80 nm thick either with or without cross striation, as well as in microfibrills. Collagen of the III type in the intercellular substance of the arterial wall occurs in nonfibrillar form. Collagen of the IV type is revealed in basal membranes of the smooth muscle cells of the arterial wall, of the muscle fibers and of endothelium of blood capillaries of the skeletal muscle. Collagen of the V type is found as accumulations having various size and form; they localize in many places of the intercellular substance of the arterial wall. A tight contact is revealed between the formations including collagen of the V type with drops of elastin and elastic fibers. A suggestion is made that collagen of the V type participates in formation of elastic fibers.

[Distribution of collagen types I, III, IV and V in the walls of human arteries]. / Raspredelenie kollagena I, III, IV, V tipov v stenke arterii cheloveka.

Using immunofluorescence the localization of I, II, IV, V type collagen in different layers of the artery wall was established. The adventitia was shown to contain only I and III type collagen. All collagen types studied were identified in the media. The structural organization and quantity of different types of collagen were found to depend on the artery caliber. The distribution of I, III, IV, V type collagen in the aortal intima is described. The localization of athrombogenic collagen of type IV and V in the area of the endothelial basal membrane is highlighted. The authors revealed the presence of I and III type collagen in the subendothelium and the age-related increase in interstitial collagen levels in the intima which is important for predicting thrombosis in deendothelization . Employing immunoelectron microscopy, previously undescribed forms of I, III, IV, V type collagen organization into microgranular structures were ascertained.

[Formation and accumulation of myelin bodies and other membrane structures in the arterial wall in man in atherosclerosis]. / Obrazovanie i nakoplenie mielinovykh telets i drugikh struktur v arterial'noi stenke chelovek pri ateroskleroze.

Unaltered areas and fibrolipid plaques of various human arteries were examined electronmicroscopically. Myelin bodies were found to be produced by smooth-muscle cells of the intima and media of unaltered parts of the arterial wall. The formation of myelin bodies by smooth-muscle cells significantly increases in the fibrolipid plaques. Myelin bodies are frequently located in the cytoplasm matrix of altered smooth-muscle cells, in the areas of myofilament lysis. They are also found within mytochondria and in the cystern lumina of the granular cytoplasmatic reticulum. The accumulation of membranous structures in the fibrolipid plaques results from myelin-body production by smooth-muscle cells and vacuoles and vesicules of a varying size.