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Ataxia-telangiectasia (AT) cells are hypersensitive to the lethal effect of gamma-rays, whereas little or no gamma-ray induced mutation has been observed. In this work, exposure to gamma-rays of an Epstein-Barr virus-transformed AT lymphoblastoid cell line, GM2783, resulted in a clear dose-dependent increase of mutation for 6-thioguanine resistance.

Diethylstilbestrol, a unique carcinogen lacking measurable mutagenic potency in Salmonella, was shown to be an inhibitor of microtubule assembly in vitro using microtubule proteins isolated from porcine brains. The effective concentration of diethylstilbestrol was 10-200 microM, as determined by viscometry, turbidity measurement, and electron microscopic analysis.

The growth of rat ascites hepatoma cells (AH 66) in vitro was inhibited and the amount of alpha-fetoprotein (AFP) in the culture medium was increased in the presence of dibutyryl adenosine 3'-5' cyclic monophosphate (DBc-AMP). Electronmicroscopically, AH 66 cells that had been incubated with DBc-AMP showed an increase in polysomes on rough endoplasmic reticulum (RER), and some mitochondria appeared to be completely surrounded by RER. AFP in untreated cells was found to be localized on ribosomes of RER, free ribosomes and occasionally also on microvilli of cell membranes by electronmicroscopic and immunohistochemical analysis. After DBc-AMP treatment, increased staining of AFP was identified on ribosomes of RER and microvilli of cell membranes as well as on nuclear membranes. These results suggest that DBc-AMP accelerates the production and release of AFP in cultured rat ascites hepatoma cells.

The subcellular distribution of sialidase in rat hepatoma induced by 3'-methyl-4-dimethylaminoazobenzene was studied by using sialyllactose as a substrate in the pH range of 4.0-7.0. As found in rat liver, the activity was recovered largely in the mitochondrial/lysosomal fraction with an optimal pH of 4.5 and in the cytosolic fraction with an optimal pH of 6.0, although hepatoma lysosomal (acidic) sialidase was also distributed in the microsomal fraction. The lysosomal and cytosolic sialidases of the hepatoma were indistinguishable from the corresponding enzymes of liver in chromatographic behavior, kinetics and substrate specificity. The levels of lysosomal and cytosolic sialidase activities in liver and hepatomas were then studied in the pellet and supernatant fractions, respectively, obtained by centrifuging the postnuclear supernatant at 105,000g for 1 hr. All the hepatomas tested, one primary and three transplanted, showed higher lysosomal sialidase and lower cytosolic sialidase activities as compared with liver. Quantitative changes similar to those seen in hepatomas were observed in regenerating liver after partial hepatectomy.

The effect of caffeine on the development of hepatic tumors induced by 2-acetylaminofluorene (2-AAF) was studied in 6-week-old male ACI rats. Rats in group 1 were fed a diet containing 0.02% 2-AAF for 18 weeks and then basal diet for 15 weeks with normal drinking water throughout. Animals in group 2 received a diet containing 0.02% 2-AAF and a solution of 0.2% caffeine as their drinking water for 18 weeks, followed by basal diet and caffeine-free water. Rats in group 3 received drinking water containing 0.2% caffeine for 18 weeks. Rats in group 4 were given a basal diet and water freely and served as controls. The experiment was terminated after 33 weeks. Both the multiplicity, i.e. the number of tumors per rat, and the size of tumors were less (P less than 0.001 in the former case, by Student's t-test) in group 2 than in group 1. Thus, the induction of tumors of the liver by 2-AAF was suppressed by the administration of caffeine.

The effect of sodium chloride on the promotion stage of gastric carcinogenesis by N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) was studied in male inbred Wistar rats. Rats in group I were given MNNG at a concentration of 50 micrograms/ml in their drinking water for 12 weeks and then 1 ml of saturated NaCl solution intragastrically once a week until experimental week 65. Rats in group II were given MNNG for 12 weeks and then 1 ml of distilled water intragastrically once a week until week 65. Rats in group III were not treated for the first 12 weeks and were then given 1 ml of saturated NaCl solution intragastrically once a week until week 65. The incidence of adenomatous hyperplasias in the glandular stomach was significantly higher in group I than in group II, but the incidences of gastric adenocarcinomas and adenomas in groups I and II were not significantly different. No neoplastic or preneoplastic changes were observed in the stomach in group III.

A novel human cultured cell line, P39/Tsugane, was established from leukemic cells in the peripheral blood of a 69-year-old male with overt leukemia following myelodysplastic syndrome (MDS). P39/Tsugane cells were characterized by blastic appearance, presence of NaF-sensitive alpha-naphthyl butylate esterase activity, Fc gamma-receptor, C3-receptor, capacity to phagocytize sensitized erythrocytes, and reactivity with monoclonal antibodies such as OKT4, My4, VIMD5, MCS-2 and My7. These data indicate that P39/Tsugane cells are of myelomonocytoid nature. P39/Tsugane had a hypodiploid chromosome constitution with a gain of a consistent marker, 6q+, the presence of less consistent markers 9q+ and rcp(14;16), and random and non-random losses of autosomes: in accordance with the reported cytogenetic profiles of MDS, a representative karyotype of the present cell line is 45,XY,+del(6)(q15),9q+, t(14;16)-(q24;q21),-16,-17. P39/Tsugane cells were transplantable intraperitoneally into nude mice, and produced abdominal tumors and hemorrhagic ascites. These results indicate that P39/Tsugane is the first cultured cell line of myelomonocytoid nature to be derived from overt leukemia following MDS. Therefore, P39/Tsugane cells should be useful for studies on the differentiation of leukemia cells, the pathogenesis of MDS and in vitro-in vivo experimental chemotherapy.

Two distinct cell lines were obtained from a single heterotransplanted tumor which had originated from a primary focus of small cell carcinoma of the lung (SCCL). They were maintained separately from the beginning in culture media with and without fetal calf serum supplementation. Cells in the serum-free medium grew mostly floating in loose aggregates and showed poor cell cohesiveness, scanty cytoplasm and a few intracytoplasmic small dense-cored granules; all of these features are characteristics of oat cell type SCCL. On the other hand, cells in the serum-supplemented medium grew mostly floating in flatter and more closely associated clumps, were larger, and showed increased cell cohesiveness, occasional tubular structures, better developed organelles including dense-cored granules, and an increased number of cell attachments; these features are characteristics of intermediate cell type SCCL. The modal number of chromosomes differed from each other. Neuron-specific enolase (gamma enolase) and aromatic L-amino acid decarboxylase (ADC) activities in cell pellets were significantly higher in both lines than in control non-small cell lung cancer cell lines. The alpha/gamma type enolase ratio was lower, as was the ADC activity, in serum-free cultures than in serum-supplemented cultures. Interchange of the culture medium induced changes of the growth pattern and cell type from "oat cell type" to "intermediate cell type" and vice versa. The chromosomal number also partially changed. These findings suggest that cultured cells of SCCL alter their growth pattern and cell type depending on the culture conditions and that the selective growth of one cell type might then take place.

The incidence of anti-adult T-cell leukemia-associated antigens (ATLA) was surveyed in 134 patients under chronic hemodialysis in the Nagasaki area, as well as 4708 blood donors resident in the same area as controls: 23 patients (17%) and 201 donors (4.3%) were positive for anti-ATLA antibody. All seropositive patients were found to have had a positive history of blood transfusions. Seroconversions were confirmed in 9 cases, all of them after initiation of transfusions. In total, 216 units of blood were transfused in 7 seroconverted patients, and this is consistent with the estimated rate of anti-ATLA antibody-positive donor blood supplied by the Red Cross Nagasaki Blood Center (5%).

A new type of ionizing radiation-induced DNA base damage, 8-hydroxyguanine formation, was found in DNA that had been irradiated by X-rays in aqueous solution. The extent of this modification linearly increased with increase in the X-ray dose up to 40 krad. When an OH radical scavenger, ethanol, was added to the DNA solution, the hydroxylation was inhibited almost completely, suggesting that the reaction proceeds via the formation of OH radicals.