Hematopoietic Tissue

Fohc acid is a precursor of several important enzyme cofactors required for the synthesis of nucleic acids (qv) and the metaboHsm of certain amino acids. Fohc acid deficiency results in an inabiUty to produce deoxyribonucleic acid (DNA), ribonucleic acid (RNA), and certain proteins (qv). Megaloblastic anemia is a common symptom of folate deficiency owing to rapid red blood cell turnover and the high metaboHc requirement of hematopoietic tissue. One of the clinical signs of acute folate deficiency includes a red and painhil tongue. Vitamin B 2 folate share a common metaboHc pathway, the methionine synthase reaction. Therefore a differential diagnosis is required to measure foHc acid deficiency because both foHc acid and vitamin B 2 deficiency cause... 

Kucia M, Wojakowski W, Reca R, Machalinski B, Gozdzik J, Majka M, Baran J, Ratajczak J, Ratajczak MZ (2006) The migration of bone marrow-derived non-hematopoietic tissue-committed stem cells is regulated in an SDF-1-, HGF-, and LIF-dependent manner. Arch Immunol Ther Exp (Warsz) 54 121-135... 

Damage to the skeleton, hematopoietic tissue of the bone marrow, and epithelial tissues closely apposed to the skeleton has been noted in animals administered 144Ce in relatively soluble forms by inhalation or injection. At relatively early times after exposure the major target organ has been the bone marrow while at later times all three tissues have shown effects of the radiation damage from the l44Ce deposited in the skeleton. 

Is associated with tissue structure and pathology of kidneys, liver, gills, and other hematopoietic tissues... 

Reduced growth, reduced brain weight, abnormal skeletal development, ALAD depressions in hematopoietic tissues, elevated burdens (mg/kg fresh weight) in kidney (7), and liver (4)... 

O. mykiss 5-80 Juveniles exposed for 28 days had alterations of renal corpuscles and renal tubules at 5, 10, 20, or 40 pg/L exposures necrosis of endothelial cells and renal hematopoietic tissue were prominent at 80 pg/L 17... 

Shinozuka, J. et al. T-2 toxin-induced apoptosis in hematopoietic tissues of mice. Toxicol. Pathol. 26, 674, 1998. 

Faust, N., et al. Different macrophage populations develop from embryonic/fetal and adult hematopoietic tissues, Exp. Hematol., 25, 432, 1997. 

Rose, W.L. et al., DNA adducts in hematopoietic tissues and blood of the mummichog, Fundulus heteroclitus, from a creosote-contaminated site in the Elizabeth River, Virginia. 

Bone Marrow The soft tissue filling the cavities of bones. Bone marrow exists in two types, yellow and red. Yellow marrow is found in the large cavities of large bones and consists mostly of fat cells and a few primitive blood cells. Red marrow is a hematopoietic tissue and is the site of production of erythrocytes and granular leukocytes. Bone marrow is made up of a framework of connective tissue containing branching fibers with the frame being filled with marrow cells. [NIH]... 

Since numerous DUBs are present in eukaryotic organisms (Table 2), it is probable that they possess substrate specificity. UCHs have been studied in some detail with respect to their substrate specificity. Two major UCHs in mammals are UCH-Ll and UCH-L3. Larsen et al showed that UCH-Ll cleaves linear polyubiquitin molecules more efficiently than UCH-L3. In contrast, UCH-L3 appears to prefer ubiquitin fused to small ribosomal proteins (see Figure 7). The tissue distribution of the two UCHs is indicative of their functional specialization as well. UCH-Ll is a neuronal-specific enzyme whereas UCH-L3 is expressed primarily in hematopoietic tissues. Another UCH called UCH-L2 has wide tissue distribution. ... 

J,l/mouse, twice a week for 25 weeks, to female ICR mice produced forestomach tumors (squamous cell carcinoma and papilloma), lung tumors (adenocarcinoma and adenoma), and tumors of the hematopoietic system (thymic lymphosarcoma and lymphatic leukemia), with dose-related response by 18 months. It was concluded that the target organ of benzotrichloride carcinogenesis in mice is the local tissue that is primarily exposed and the lung and hematopoietic tissue when administered systemically. 

In a group of uranium mill workers, there was an excess of deaths from malignant disease of lymphatic and hematopoietic tissue data from animal experiments suggested that this excess may have resulted from irradiation of lymph nodes by thorium-230, a disintegration product of uranium. Some absorbed uranium is deposited in bone. A potential risk of radiation effects on bone marrow has been postulated, but extensive clinical studies on exposed workers have disclosed no hematologic abnormalities. ... 

A significantly (p<0.05) increased incidence of malignancies in the lymphatic and hematopoietic tissues of uranium mill workers (cohort of 662 males) was found by Archer et al. (1973). The radioactivity in the tracheobronchial lymph nodes of the workers was found to be primarily the result of alpha emissions from thorium-230 and not from uranium-234 or uranium-238. Consequently, the authors suggested that the increased incidence of malignancies may have been a result of thorium-230 exposure and not uranium exposure. Exposure levels of thorium were not reported therefore, the results of the study are not reported on Table 2-1 or plotted in Figure 2-1. 

Prockop DJ. Marrow stromal cells as stem cells for non-hematopoietic tissues. Science 1997 276 71-74. 

Production of blood cells in bone marrow of the central axial skeleton is referred to as medullary hematopoiesis. Hematopoietic tissue in adult bone marrow is well perfused and contains fat cells (adipocytes), and various types of blood and blood precursor cells encased within a protein matrix. Fibroblast, stromal and endothelial cells within bone marrow, serve as sources of matrix proteins as well as a factory for growth factors and chemokines that regulate blood cell production and release matured cells into the circulation [2,3]. Chemokines act as signal lamps for trafficking of lymphocytes in and out of lymphoid tissues. Erythroblasts, neutrophils, lymphoblasts, macrophages, megakaryocytes, and pluripotent stem cells are also found within the calcihed lattice crisscrossing the marrow space. 

Thiouric acid is formed by XO and is excreted renally. Whereas the cytosolic enzyme TPMT is expressed ubiquitously in humans [e.g., in the intestine, liver, red blood cells (RBC) and white blood cells], XO is not expressed in hematopoietic tissue (94). Therefore, TPMT-dependent methylation is critical in white blood cells, leading to an enhanced cytotoxic effect in patients with low TPMT activity. 

In the well-conducted, comprehensive 90-day studies, no treatment-related grossly or histologically observable lesions were found in the lungs, hearts, hematopoietic tissues, or in the skin or eyes of rats and mice dosed by gavage with isophorone (NTP 1986), rats treated with isophorone in the diet... 

Irons, R.D., Stillman, W.S. Cloyd, M.W. (1987a) Selective activation of endogenous ecotropic retrovirus in hematopoietic tissues of B6C3Fi mice during the preleukemic phase of 1,3-butadiene exposure. Virology, 161, 457-462... 

The relatively high expression of pi 15-RhoGEF/Lsc in hematopoietic tissues (Hart et al, 1996 Whitehead et al., 1996) suggested a specialized function for this protein. Indeed, the locus for this protein in mice can be knocked out without apparent gross effects on mouse development, survival, and reproduction (Francis et al., 2006 Girkontaite et al., 2001). 

Benzene affects the hematopoietic tissue in the bone marrow and also appears to be an immunosuppressant. There is a gradual decrease in white blood cells, red blood cells, and platelets, and any combination of these signs may be seen. Continued exposure to benzene results in severe bone marrow damage and aplastic anemia. Benzene exposure has also been associated with leukemia. 

Systemic Effects. Diseases of the hematopoietic tissues have been reported in patients given repeated injections of radium-224. Anemia, panmyelophthisis, and chronic myeloid leukemia were seen in excess of the control levels in these cases (compared with a higher incidence of acute leukemia in the control group) (Wick et al. 1986). Anemia has also been reported in case studies of the radium dial painters (Martland 1931), but the disease patterns have not been clearly established (Sharpe 1974). 

Jeffery EH, Abreo K, Burgess E, et al. 1996. Systemic aluminum toxicity Effects on bone, hematopoietic tissue, and kidney. J Toxicol Environ Health 48 649-665. 

TCDD, a dermal LD50 value in rabbits was calculated as 275 g/kg (Schwetz et al. 1973). Deaths occurred within 12-22 days, but the cause of death was not specifically indicated. Decreased survival was observed in Swiss Webster mice exposed 3 days a week to 2,3,7,8-TCDD at 0.05 g for 13 weeks and 0.001 g for chronic duration (NTP 1982a). In the subchronic study (NTP 1982a), male mice exhibited a higher mortality rate than females lethal doses in males caused marked effects in lymphoid and hematopoietic tissues as well as on the liver and lung. The cause of death in the chronic study (NTP 1982a) was not specified. No increase in lethality was reported in HRS/J hairless mice dermally exposed to 0.0025 g, 2 days a week, for 20 weeks (Hebert et al. 1990). 

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