[Side effect of granulocytic colony-stimulating factor on the structure and function of mouse liver].

AIM: To study effects of granulocytic colony-stimulating factor (G-CSF) on morphology and function of mouse liver. MATERIAL AND METHODS: G-CSF was injected subcutaneously to mice in a daily dose 200 mcg/kg for 8 days. Peripheral blood formed elements percentage was estimated 24 hours, 7 and 28 days after the last injection of G-CSF. Bilirubin level, activity of aspartate- and alaninaminotransferase (AST, ALT) were studied in the blood serum. Structure of hepatic parenchyma was studied on histological sections stained with hematoxilin-eosine. The sections were stained with picro-sirius red for detection of collagen. RESULTS: G-CSF raised the count of neutrophilic granulocytes in peripheral blood. Maximal number of neutrophils in blood was observed on day 7 after discontinuation of G-CSF. At the same time, hepatocytes were dystrophic and partially necrotic. The lumina of many vessels of hepatic lobules were filled with erythrocytes. Going in parallel hemolysis of erythrocytes corresponded to biochemical indices of functional activity of the liver. Content of AST, but not ALT, increased 2-3-fold. Vascular walls were thick due to active synthesis of collagen. Four weeks after the last G-CSF injection vascular lumina were free of blood, but vascular epithelium layer was thick. CONCLUSION: Side effects of G-CSF were found. They affected physiological status of mouse liver causing necrosis of hepatosytes, venous plethora and red cell hemolysis. Maximal changes were registered on day 7 after discontinuation of G-CSF. The inflammatory process (collagen synthesis) continues after 4 weeks upon discontinuation of G-CSF.

[Hematopoietic stem cells (CFUc) in athymic mice. II. The morphological composition of splenic colonies formed by 11-day-old CFUc from the bone marrow of thymectomized mice]. / Stvolovye krovetvornye kletki (KOEc) u timusdefitsitnykh myshei. II. Morfologicheskii sostav selezenochnykh kolonii, obazovannykh 11-sutochnymi KOEc iz kostnogo mozga timéktomirovannykh myshei.

The author studied the effect of the animal's age and marrow donor's thymectomy on differential potentials of CFUc by morphological structure of the splenic colonies. Bone marrow from thymectomized mice (TEM) was examined 1-25 months after thymectomy. Intact age-matched animals served control. The age of mice-donors had no influence on morphological types of the colonies formed by the marrow injected i. v. to irradiated recipients. TEM marrow developed all types of colonies known (erythroid, granulocytic, megakaryocytic, non-differentiated and mixed), though their percentage differs from the control. This is true for 11-day, but not for 8-day colonies. Among the 11-day colonies formed by TEM marrow the portion of megakaryocytes increased 3-fold, while mixed colonies were slow in formation when compared to the control.

[Hematopoietic precursor cells in radiation chimeras restored by bone marrow from thymectomized mice]. / Krovetvornye kletki-predshestvenniki u radiatsionnykh khimer, vosstanovlennykh kostnym mozgom timéktomirovannykh myshei.

Radioprotective capacity of bone marrow CFUs of adult thymectomized mice was studied. Lethally irradiated mice were inoculated with bone marrow of mice thymectomized 8-11 months before. The colony forming capacity and proliferative rate of CFUs were studied 1-7.5 months after obtaining the radiation chimeras. It has been shown that proliferative capacity of bone marrow of adult thymectomized mice was reduced in comparison with that of normal animals. It is related to the decrease (4-fold) of the proliferative rate of bone marrow of thymectomized mice which was inoculated into lethally irradiated recipients 1 month before. We also found that the content of CFUs in bone of those chimeras was reduced later--after 7.5 months. In this period (1-7.5 months) the cellularity of bone marrow did not change.

[The proliferative potential of CFUs from the bone marrow of thymectomized mice]. / Proliferativnyi potentsial KOEs iz kostnogo mozga timéktomirovannykh myshei.

Proliferative potential of CFUs in bone marrow of young and adult mice (1.5-25 months) and thymus influence on this property were studied. It has been shown on the model of adult thymectomized mice that during "steady state" hematopoiesis, proliferative potential of bone marrow CFUs does not depend on the animals age and on thymic factors.

[Repair of the radiation damage in hematopoietic stem cells from the mouse embryonic liver. Kinetic aspects]. / Reparatsiia radiatsionnykh povrezhdenii v stvolovykh krovetvornykh kletkakh iz émbrional'noi pecheni myshi. Kineticheskie aspekty.

The method of fractionated irradiation was used to study kinetic aspects of repair of sublethal radiation damages in precursor cells from mouse embryonal liver that form in vivo colonies on 8th and 11th days. It was shown that 11-day CFUs had a lesser ability to repair sublethal radiation damages than 8-day ones at different time-intervals between radiation fractions (from 2 to 6 h). These two CFUs sub-populations differed also in the repair kinetics.

[Kinetics of reparation of sublethal radiation damage in early hematopoietic precursors]. / Kinetika reparatsii subletal'nykh radiatsionnykh povrezhdenii v rannikh gemopoéticheskikh predshestvennikakh.

The authors studied the ability of the CFU-S, forming colonies on the 8th and 11th days after bone marrow cells transplantation, to repair the sublethal radiation damages (SRD), according to Elkind's model. Special attention was given to the kinetics fo reparation for SRD for two subpopulations of CFU (8th- and 11th-days' CFU-S). the 1-6 hour intervals between two equivalent doses of irradiation were made. The ability to repair the SRD of the 11th-days' CFU-S was lower than that of the 8th-days' CFU-S at all time intervals. The maximum reparation of the 8th-days' CFU-S was observed at 5-hour period; and that was twice as high as the maximum reparation of the 11th-days' CFU-S, which was determined at 3-hour interval between the two irradiation doses.

[The 3-dimensional organization of the nucleoli of benign and malignant tumor cells from different human organs]. / Trekhmernaia organizatsiia iadryshek dobrokachestvennykh i zlokachestvennykh opukholevykh kletok razlichnykh organov cheloveka.

The method of ultrathin serial sections was used to perform a comparative ultrastructural and 3-dimensional analysis of nucleoli for the following variants of human tumours: benign (fibroadenoma) and malignant (infiltrating ductal carcinoma) tumours of one organ (mammary gland); malignant tumours of epidermal genesis in different organs (squamous cell carcinomas of skin, larynx, lung, gullet, uterus); two forms of malignant tumours (squamous cell and small cell carcinomas) of one organ (lung). The spatial models of nucleoli in these tumour cells are given. The specific signs in architecture of tumour nucleoli was found. Nucleoli of fibroadenomas have well pronounced 1-4 fibrillar centres forming a united system with a lacunar component and intranucleolar chromatin. Unlike benign tumour cells, nucleoli of infiltrating ductal carcinomas are characterized by large, prominent nucleoli containing giant, multiform fibrillar centres with a complicated surface, a well developed granular component and an unusually organized lacunar system. In squamous cell carcinomas of various localization, active, hypertrophied nucleoli with pseudonucleolonemal organization were found. The small cell carcinoma of lung differs from the squamous cell cancer of the same organ by dense, fibrillar nucleoli with a small amount of granular component located on the periphery of the nucleolar body. Nucleolar type reflecting the functional state of malignization process may serve as an additional diagnostic criterion for tumour identification.

[Cellular repair of sublethal radiation damage in 2 subpopulations of the CFUs from embryonal liver and bone marrow of adult mice]. / Kletochnaia reparatsiia subletal'nykh radiatsionnykh povrezhdenii dvukh subpopuliatsii KOEs iz émbrional'noi pecheni i kostnogo mozga vzroslykh myshei.

The authors studied the ability of the CFU-s, forming colonies on the 8 and 11 day after transplantation of cells from fetal liver (FL) of 14-18 day gestation and adult mouse bone marrow (BM), to repair the sublethal radiation damages (SRD), according to Elkind's model. The ability to repair the SRD of 11-day CFU-s (both EL- and BM-derived) was lower than the ability of 8-day CFU-s. Both subpopulations of CFU-s (as 8-, as 11-day) from FL have a reduced index of SRD reparation as compared with the corresponding meanings for BM.

[Comparison of the reparative property of early and late CFUs after sublethal radiation injury]. / Sravnenie sposobnosti rannikh i pozdnikh KOEc k vosstanovleniiu posle subletal'nykh radiatsionnykh povrezhdenii.

Restoration ability of early and late CFUs has been studied using bone marrow sublethal fractional irradiation. It has been shown that CFUs capacity for early postirradiation repair on the 11th day is sharply reduced, as compared to that of CFUs on the 8th day.

[Effect of the thymus on the capability of stromal progenitor cells for intracellular repair of radiation damage]. / Vliianie timusa na sposobnost' stromal'nykh kletok-predshestvennikov k vnutrikletochnoi reparatsii radiatsionnykh povrezhdenii.

Cells-precursors of haemopoietic microenvironment, as well as osteogenic cells-precursors, indicated with heterotopic transplantation of mouse bone marrow, can repair sublethal radiation damages. Thymectomy of the bone-marrow donors does not influence this capacity of the stromal precursors.

[Early postradiation recovery of precursor cells of the hemopoietic stroma]. / Rannee postradiatsionnoe vosstanovlenie kletok-predshestvennikov krovetvornoi stromy.

The author studied the ability of stromal precursor cells of mouse bone marrow to intracellular repair of radiation-induced injuries. It was shown that the slow-restorable, highly radioresistant population of stromal precursor cells is capable of early post-radiation recovery.

[Progenitors of transitory spleen colonies in mouse embryonal liver]. / Predshestvenniki tranzitornykh selezenochnykh kolonii v émbrional'noi pecheni myshi.

The transitory nature of about half of spleen colonies macroscopically detectable in the spleen 7 days after injection of embryonal liver hemopoietic cells was demonstrated by localization of the colonies on the spleen surface and by the study of the content of polypotential and unipotential precursors in individual 7- and 11-day colonies produced in the spleen of irradiated mice by the cells of early (12-13-day) and late (17-18-day) embryonal liver.

[Effect of the thymus on hematopoietic stem cells and on their capacity for self-maintenance]. / Vliianie timusa na stvolovye krovetvornye kletki i na ikh sposobnosti k samopodderzhaniiu.

The hemopoietic cell cloning in the spleen of irradiated mice showed that thymectomy in mature animals produced no significant changes either in the CFU count or in their self-maintenance ability.