[Effect of reduced glutathione on N-butyl-N-(4-hydroxybutyl)-nitrosamine-induced urinary bladder cancer in rats].
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Biomedical subjects
Publications and source records attributed to Y Honma.
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We developed a short term assay for screening promoters of bladder cancer. This assay, in which maintenance of concanavalin A-agglutination of isolated rat bladder cells induced by subcarcinogenic treatment with bladder carcinogen is measured, suggested the possible promoting effects of L-isoleucine, L-leucine, D-tryptophan, and L-valin. Long term in vivo carcinogenesis experiments were carried out on L-isoleucine and L-leucine and it was shown that both were, in fact, promoters of bladder cancer in rats.
Variant subpopulations of FM3A mouse mammary carcinoma cells that have increased lung-colonizing potential were obtained previously by sequentially harvesting pulmonary metastases, culturing their cells in vitro, and reestablishing the metastases in vivo. In the present study, glycosaminoglycan production by the parental and variant cells was studied after metabolic labeling of cultures by [14C]glucosamine for 24 hr. Analysis of the products indicated that the rate of incorporation of the labeled precursor into hyaluronic acid in the high-metastatic variant cells was 27 to 54 times the rate in the low-metastatic variant cells and that the increase in hyaluronic acid synthesis was not associated with an increase in the rate of synthesis of other glycosaminoglycans. Both the cell layers and media of high-metastatic variants contained a much higher proportion of radioactivity in hyaluronic acid than did the corresponding fractions of low-metastatic cell lines. The results provide a basis for further investigation of the potential role of hyaluronic acid in control of the behavior of epithelial tumor cells during metastasis.
Mouse myeloid leukemia M1 cells could be induced by various inducers to form Fc receptors, phagocytize, produce lysozyme, and change into forms that were morphologically similar to macrophages and granulocytes. Previous experiments showed that change in phospholipid metabolism was associated with cell differentiation. In the present experiment, culture of M1 cells with choline analogs such as N-monomethyl-ethanolamine and N,N'-dimethylethanolamine resulted in accumulation of phosphatidyl-N-monomethyl-ethanolamine and phosphatidyl-N,N'-dimethylethanolamine in the cell membranes. This change upon treatment with choline analogs was associated with morphological and functional differentiation of the M1 cells into macrophages and granulocytes. These results suggest that phospholipid metabolism is involved in the mechanism of differentiation of M1 cells.
Changes in auditory brain stem responses were serially investigated in a patient with downward transtentorial herniation due to acute obstructive hydrocephalus to correlate the neurological signs with the results of computerized tomography. Neurological deterioration correlated highly with disruption of auditory brain stem responses, especially with that of the components of waves V to VII. A noninvasive technique, the measurement of auditory brain stem responses is thought to be useful in detecting the severity of downward transtentorial herniation and in estimating the recovery of brain stem function after surgical treatment of intracranial hypertension.
Ml cells were labeled in vitro with [3H]thymidine and injected into the peritoneal cavity of syngeneic mice. After several days the peritoneal cells were harvested and [3H]labeled cells were determined by autoradiography. The inoculated isotope-labeled Ml cells differentiated in the peritoneal cavity and lipopolysaccharide, an inducer of cell differentiation, significantly stimulated differentiation. These results provide direct evidence that Ml cells can be induced to differentiate in vivo under conditions in which leukemia can develop.
Mouse myeloid leukemia cells (Ml) were induced to differentiate into macrophages and granulocytes by various inducers including glucocorticoid. The tumour promoter 12-O-tetradecanoylphorbol-13-acetate (TPA) inhibited the induction of differentiation of Ml cells in medium containing calf serum, but enhanced the induction in medium containing fetal calf serum and several inducers. For elucidation of the factor(s) in serum affecting the response of Ml cells to tumour promoters, calf serum was fractionated by Sephadex G-200 gel filtration. Differentiation of Ml cells induced by dexamethasone was markedly inhibited by TPA and high mol. wt fractions of calf serum eluted in the void volume and low mol. wt fractions that co-migrated with bovine serum albumin. High mol. wt fractions alone inhibited the differentiation of Ml cells induced by dexamethasone, and also acted additively with TPA in inhibiting the differentiation. The inhibition by high mol. wt fractions was not related to cytotoxicity and was reversible. The differentiation of Ml cells induced by proteinous inducer or lipopolysaccharide was also inhibited by high mol. wt fractions. The inhibitory factor was heat stable (70 degrees C for 20 min or 90 degrees C for 10 min). These results suggest that the tumour promoter and calf serum components cooperate in inhibiting differentiation of mouse myeloid leukemia cells induced by various inducers.
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The ironfish considered to be the natural hybrid between the Funa (Carassius carassius) and goldfish (C. auratus), has several peculiarities in its morphology, karyology and reproductive biology. Its adenohypophysis also shows follicular formations which are never found in either parent species. The follicles of the ironfish adenohypophysis consist of both prolactin cells and stellate (agranular) cells. The prolactin cells have a tall pyramidal form, and their secretory granules are seen more often in the basal cytoplasm than in the apical region. The electron-dense content of the granule is released into the perifollicular space by exocytosis. The apices of the cells bearing microvilli and a cilium are exposed to the follicular lumen. Many of the cilia, however, protrude from the lateral surface of the apical region into the intercellular cleft. The apical processes of the stellate cells extend among the prolactin cells and reach the follicular lumen. The end of the process becomes broad with microvilli and a cilium, and is joined together with the apical processes of other stellate or prolactin cells and sometimes lies in close proximity to the corticotrophs near the follicle. Nerve terminals in the perifollicular region contain small clear vesicles and large granular vesicles. They are occasionally in direct contact with prolactin cells and corticotrophs. By fluorescence histochemistry for catecholamines, blue-green fluorescent fibers are frequently detected in the RPD but rarely near the follicle. These findings suggest that the follicles seen in the ironfish are derived from the regional rudiments of the Rathke's pouch.
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The tumor promoter TPA inhibited both functional and morphological differentiation of mouse myeloid leukemia M1 cells cultured in medium containing calf serum or horse serum, but enhanced these inductions in medium containing fetal calf serum. The metabolic processes of prostaglandin E2 synthesis were associated with modification by TPA of differentiation of M1 cells. The factor(s) in the sera affecting the differentiation of M1 cells with TPA was nondialyzable and macromolecular. Upon Sephadex G-200 gel filtration, much more inhibitory activity was found in calf serum than in fetal calf serum, and stimulatory activity was found only in fetal calf serum.
In medium with serum, 12-O-tetradecanoylphorbol-13-acetate (TPA) induced alpha-naphthyl acetate esterase activity in human promyelocytic leukemia cells (HL-60), adherence of the cells to the culture dish, and their change into forms that were morphologically similar to macrophages. HL-60 cells grew in the absence of serum in synthetic medium supplemented with insulin, transferrin, and several trace elements, and could be maintained for more than 6 months in this medium. Induction of differentiation by TPA was observed with cells grown in serum-free medium. Human myeloid leukemia cells (K562-4) cultured in medium with serum could not be induced to differentiate even in the presence of TPA, but their differentiation into macrophages in the presence of TPA, arginase or actinomycin D was observed after they had been grown in serum-free medium for 4 months. Addition of serum inhibited the induction of differentiation of HL-60 and K562-4 cells that had been grown in serum-free medium. Calf serum was more inhibitory than fetal calf serum on TPA-induced differentiation, but there was no significant difference in the effects of the two sera on induction by actinomycin D or arginase. These results suggest that the different responses in media with different sera may be specific to TPA. Induction of adhesiveness of K562-4 cells by TPA required some unknown serum factor(s), although addition of serum inhibited the inductions of morphological and functional differentiation. The relation between the ability of K-562-4 cells to be induced to differentiate into macrophages and long-term cultivation in serum-free medium is discussed.
Mouse myeloid leukemia M1 cells were induced to differentiate in vitro into macrophages and granulocytes by various inducers, including dexamethasone. Prostaglandin F2 alpha inhibited the inductions by dexamethasone of phagocytic and lysozyme activities in M1 cells. Prostaglandin F2 alpha stimulated the production of differentiation-inhibiting activity (I-activity) in M1 cells. I-activity production by prostaglandin F2 alpha was decreased by simultaneous treatment with actinomycin D (5 ng/ml) but not with 5-fluoro-2'-deoxyuridine (10 ng/ml). The I-activity was inactivated by heating (70 degrees, 20 min) or by treatment with trypsin but not with mixed glycosidases or ribonuclease, suggesting that I-activity was due to a proteinous substance(s). B-Type prostaglandins also stimulated I-activity production, whereas A-, E- and D-type ones did not. Induction of prostaglandin E2. Retinoic acid stimulated the synthesis and release of prostaglandin F2 alpha and production of I-activity in M1 cells. Indomethacin completely inhibited induction of I-activity by retinoic acid. On the basis of these results, the relationship between I-activity production and prostaglandin F2 alpha production is discussed.
The effects of conditioned media (CM) of various clones of mouse myeloid leukemia cells (M1) on colony formation of normal mouse bone marrow cells were examined under various conditions. The CM of sensitive M1 cells, which could be induced to differentiate into macrophage-like and granulocyte-like cells by various factors stimulating the differentiation (D-factor), slightly inhibited colony formation of normal bone marrow cells by colony stimulating factor (GM-CSF). The CM of resistant M1 cells, which were resistant to the induction of differentiation even with high concentrations of the D-factor, significantly inhibited the colony formation of bone marrow cells by GM-CSF. The inhibitory activity of the CM from resistant cells decreased on treatment of the cells with a low concentration of actinomycin D, which could sensitize the resistant cells to induction of differentiation. The CM of differentiated sensitive M1 cells induced by dexamethasone stimulated the colony formation of bone marrow cells without exogenously added GM-CSF. Most of the GM-CSF activity in the CM was separated from the D-factor of M1 cells by Sephadex G-75 gel filtration.
The effects of amino acids on the enhanced agglutinability of bladder cells with concanavalin A induced by subcarcinogenic treatment with N-butyl-N-(4-hydroxybutyl)nitrosamine were examined. The amino acids examined were L-alanine, L-arginine, L-asparagine, L-aspartic acid, L-cysteine, L-glutamic acid, L-glutamine, L-glycine, DL- and L-histidine, L-hydroxyproline, L-isoleucine, D- and L-leucine, L-lysine, L-methionine, DL- and L-phenylalanine, L-proline, L-serine, L-threonine, DL-, D- and L-tryptophan, L-tyrosine and D- and L-valine. They were added to powdered diet at a concentration of 2.0%. L-Leucine, L-isoleucine, L-valine, DL- and D-tryptophan prolonged the period during which the bladder cells showed enhanced agglutinability with concanavalin A. Leupeptin, a protease inhibitor, and L-leucyl-L-leucine were also examined at a concentration of 0.1% because of their similar chemical structures, and were found to have the same effect. The tumor-promoting effects of DL-tryptophan and leupeptin have already been established by in vivo carcinogenesis experiments. The effects of L-leucine, L-isoleucine, L-valine, D-tryptophan and L-leucyl-L-leucine, detected by this short term assay, suggest that these compounds may also be promoters of bladder cancer in rats.
Mouse myeloid leukemia cells (M1) could be induced by various inducers to differentiate into macrophages and granulocytes. When M1 cells were cultured with inducer, the incorporation of methyl group into phosphatidylethanolamine was decreased while the incorporation of choline into phosphatidylcholine was slightly increased. The decrease of cellular phospholipid methylation may be partly due to the decrease of methyltransferase activity.