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Biomedical subjects

M Umeda

Publications and source records attributed to M Umeda.

At least 469 records · Page 26Linked to original sources

Cytotoxic and mutagenic effects of sterigmatocystin on cultured Chinese hamster cells.

Cytotoxic and mutagenic effect of sterigmatocystin (STC), a carcinogenic mycotoxin, on cultured Chinese hamster cells were investigated in the presence or absence of a metabolic activation system. STC directly applied to the cells induced cytotoxicity and drug-resistant mutations in a time- and concentration-dependent manner. Analyses of the effects of STC showed that treatment for shorter periods was more effective than that for longer periods. The presence of an activation system, cytotoxic and mutagenic effects of STC were strongly enhanced, and 1% of the microsome fraction was most efficient in inducing the effects. Analyses by equitoxic comparison showed that there was little difference in mutagenic activity between the direct treatment and the treatment using an activation system.

Animals↗

Mycotoxin production by Chaetomium spp. and related fungi.

Screening for mycotoxin production by Chaetomium spp. and related fungi on rice culture was conducted by a combination of cytotoxicity tests using HeLa cells and thin-layer chromatography. Producers of sterigmatocystin, O-methylsterigmatocystin, chaetochromin, chaetocin, chetomin, cochliodinols, and mollicellin G were found and the taxonomic significance of these findings is discussed.

Anti-Bacterial Agents↗

A new system of hemopoietic colony formation for permanent slides and medium changes: use of glass-fiber filters.

A new method for hemopoietic colony formation that allows the preparation of permanent slides and medium changes during the incubation period was developed in vitro. Bone marrow cells from mice were spread over glass-fiber filters, which were placed on agar medium and cultivated for 7 days. Hemopoietic colonies appeared on the glass-fibers filters. The glass-fiber filters with colonies were stained by a peroxidase and nonspecific esterase double-staining method and mounted as permanent slides. Each colony could be clearly identified and easily counted after the staining. The dose-response relationship between the number of seeded cells and the colony counts was a linear one, with the line very nearly passing through the origin on extrapolation. The colonies were classified into three types by the staining results: granuloid type, monocyte-macrophage type, and mixed type, the last containing both granuloid and monocyte-macrophage cells. Medium change during the incubation period was attempted in the experiment for phagocytic activity of the cultured cells and proved to be useful. This system appears to be useful and convenient in the study of hemopoietic colony formation.

Animals↗

Studies on the cytotoxicity, mutagenicity and chromosomal aberration-inducing activity of aclacinomycin A in cultured mammalian cells.

The cytotoxicity mutagenicity and chromosomal aberration-inducing activity of aclacinomycin A were studied using cultured mammalian cells. Aclacinomycin A was found to be a potent inhibitor of RNA synthesis in HeLa S3 cells. The survival curve in the presence of aclacinomycin A exhibited a concentration- and time-dependent cytocidal effect, and showed a sigmoidal shoulder. A cytofluorometric study suggested that aclacinomycin A caused a temporary blockage of cell cycle progression. In mutation assay using V79 cells, aclacinomycin A was shown to induce 8-azaguanine-resistant mutation, being several times more mutagenic than adriamycin. The induction of chromosomal aberrations by aclacinomycin A was also demonstrated. When cells from various sources were treated with aclacinomycin A, they were affected at a similar concentration with the exception of human normal fibroblasts, which were a little less sensitive than the others.

Aclarubicin↗

Cytomorphological study of cultured mammalian cells treated with benzaldehyde, catechol and their derivatives with special reference to inhibition of DNA synthesis.

Cytotoxicity and cytomorphological changes induced in cultured mammalian cells by the application of benzaldehyde, pyrocatechol and their derivatives were examined. Among the compounds tested, 3,4-dihydroxybenzaldehyde (protocatechualdehyde) and 1,2-dihydroxybenzene (pyrocatechol) produced cytomorphological changes characteristic of specific inhibitors of DNA synthesis in V79 cells and EJ-1 cells. However, they did not induce such changes in HeLa cells. 2,3-Dihydroxybenzaldehyde and catecholamines did not produce such characteristic changes in V79 cells. The cytological effects of protocatechualdehyde and pyrocatechol were confirmed by a study on the incorporation of 3H-precursors of DNA, RNA and protein into 3 cell lines.

Animals↗

A comparative study of assay systems for drug-resistant mutation in cultured mammalian cells.

Three assay methods which have been reported previously for the detection of drug-resistant mutation in mammalian cells were compared using V79 cells growing monolayer and FM3A cells growing in suspension. 8-Azaguanine and ouabain were used for the selection. A method in which mutagen-treated cells were replated and cultured in the control medium during expression period, followed by the incubation in a selection medium (we named immediate replating method), was more efficient for demonstrating mutated cells than other replating methods in every occasions examined. Further, the optimum expression periods by this method were shown to be 3 to 4 cell divisions after the replating on cells treated with different concentrations of a mutagen.

Animals↗

Effects of various chemicals including bile acids and chemical carcinogens on the inhibition of metabolic cooperation.

The effects of various chemicals, such as bile acids, a lectin, polyamines and chemical carcinogens, on metabolic cooperation in the hypoxanthine-guanine phosphoribosyl transferase system were surveyed. Among bile acids, lithocholic acid, chenodeoxycholic acid and ursodeoxycholic acid inhibited metabolic cooperation. However, cholic acid, deoxycholic acid and dehydrocholic acid did not. There was a structure-activity relationship among these compounds for the inhibition of metabolic cooperation. The metabolic cooperation was not inhibited by such chemicals as phytohemagglutinin, three polyamines, 7, 12-dimethylbenz [a] anthracene, N-methyl-N'-nitro-N-nitrosoguanidine, 4-nitro-quinolone 1-oxide and three biphenyl compounds. These results should be useful in relation to studies on the mechanism of inhibition of metabolic cooperation and on the relationship between this inhibitory activity and the tumor-promoting activity of various chemicals.

Animals↗

Antiproliferative activity of protocatechualdehyde on Chinese hamster cells grown in culture.

The mode of cytotoxic action of protocatechualdehyde on V79 cells was examined. The cytotoxicity of protocatechualdehyde on V79 cells was time- and cell cycle-dependent. The lethal action is selective for the cells at S phase only. The cells lethally damaged at S phase seemed to complete their DNA synthesis, although the rate of DNA synthesis became lower and the duration of S phase was prolonged. Some cells arriving at G2 phase directly entered the next S phase without cell division and died of karyorrhexis or karyolysis. Cells treated at stages of the cell cycle other than S showed normal progression of their cell cycle to the G1/S boundary. The block point of the cell cycle seemed to lie a little behind that with hydroxyurea. When the cells at phases other than S were blocked with protocatechualdehyde for 14 hr, elongation of the next S phase occurred after removal of protocatechualdehyde. On alkaline sucrose gradient analysis, little scission of parental DNA was observed in the cells treated with protocatechualdehyde.

Animals↗

Chromosomal aberrations and mutation in cultured mammalian cells induced by pyrrolizidine alkaloids.

4 pyrrolizidine alkaloids, heliotrine, lasiocarpine, petasitenine, and senkirkine, were tested for their effects of V79 Chinese hamster cells. All the alkaloids produced cytoplasmic vacuolization, and caused cellular and nuclear enlargement. Chromosomal aberrations were induced in cells treated with the alkaloids. Heliotrine and petasitenine induced interchromosomal exchanges, and lasiocarpine and senkirkine caused chromatid gaps. All the alkaloids induced an 8-azaguanine-resistant mutation in V79 cells by direct treatment for 48 h. Mutation was also induced by treatment with the alkaloids for 1 h in the presence of a metabolic activation system.

Animals↗

Chromosome aberrations induced by clinical medicines.

Inducibility of chromosome aberrations of cultured mammalian cells was examined on 11 clinical medicines which are used for a long term mainly in the field of internal medicine. P-aminosalicilic acid, isonicotinic acidhydrazid, streptomycin A, hydralazine hydrochloride methimazole and theophylline induced definite increase of chromosome aberrations. Among them P-aminosalicilic acid was a little weak in its effect. The effects of rifamycin SV, aminophylline and isosorbide dinitrate were judged as suspicious, because only a slight increase of the aberrations were caused. Reserpine and propylthiouracil induced little chromosome aberrations. Effective concentrations of these medicines in our chromosome test were compared with their maximum blood concentrations in clinical use in human quoted from the published papers. Their ratios by isonicotinic acid hydrazid, streptomycin A, methimazole, theophylline and issorbide dinitrate were very high and those by others were relatively low. Because p-aminosalicilic acid, rifamycin SV, hydralazine hydrochloride and aminophylline were positive or suspicious in our chromosome test, further pursue for the safety evaluation seems necessary.

Aminophylline↗

Cytotoxicity of methyl bromide: effect of methyl bromide on cultured mammalian cells.

Cytotoxicity of methyl bromide on cultured mammalian cells was examined. Acute toxic action was induced by methyl bromide itself and its cytotoxicity was reduced in the presence of glutathione. Its hydrolysis products or its reaction products with organic compounds in the medium was extremely low in toxicity. Although methyl bromide is known to be a methylating agent, morphological changes induced on HeLa cells were different from the changes characteristic of chemotherapeutic alkylating agents. Lethal concentration of methyl bromide on HeLa cells and primary cultured muscle, kidney and brain cells was similar (10 microgram/ml). In a detailed survey, however, there was a slight difference in the susceptibility among the cells from primary culture of brain.

Animals↗

Properties of cell lots suitable for focus assay in the chemical transformation of Syrian hamster cells in culture.

Various lots of cells obtained from Syrian hamster tissues were examined to determine their suitability for focus assay in chemical transformation in culture. Only a few lots of cells showed growth with sparse cell density during cultivation for 3 weeks without subcultivation, and not all lots of cells produced morphologically transformed foci after treatment with a carcinogen. Further, responsiveness to a tumor promotor, 12-O-tetradecanoly phorbol-13-acetate (TPA), differed among different cell lots; cell lots which induced abundant growth consisting of small spindle-shaped multilayered cells upon treatment with TPA corresponded to those in which carcinogen treatment induced transformed colonies. When TPA was applied in transformation experiments, the morphologically transformed foci grew larger in cultures maintained in the TPA medium than in cultures kept in the TPA-free medium. We suggest that cell lots which show relatively sparse cell density at confluent culture and which show abundant growth consisting of small multilayered cells upon induction with TPA are suitable for transformation assay.

9,10-Dimethyl-1,2-benzanthracene↗

Inhibition of metabolic cooperation in Chinese hamster cells by various chemical including tumor promoters.

The effects of 12-O-tetradecanoyl phorbol-13-acetate (TPA) and other chemicals on the contact-feeding phenomenon were investigated. The death of 6-TGr cells was prevented by TPA even upon culture with 3 times as many wild-type cells as in TPA-free medium. Seven out of 18 chemicals tested were shown to inhibit the phenomenon of metabolic cooperation. They were concanavalin A, lithocholic acid, chaetoglobosin A, 3-hydroxyanthranilic acid, urea, anthralin and saccharin. Among known tumor promoters, sodium deoxycholate, estradiol and phenobarbital did not inhibit the phenomenon of metabolic cooperation.

Animals↗

[Early detection of congenital hypothyroidism by TSH radioimmunoassay using filter paper blood samples (author's transl)].

It has been reported that mental retardation due to congenital hypothyroidism can be prevented by early detection and early adequate replacement therapy. We have developed a radioimmunoassay for TSH using the dried blood spot and have started screening for newborn congenital hypothyroidism using a part of sample of the inborn metabolic error screening. (1) The dried blood spot TSH of 61,000 newborn infants was assayed in the first half of our screening and that of 74,505 newborn infants was assayed in the latter half of our screening. As a result, although we were not able to detect any cases in the first screening, we were able to detect 9 cases of congenital hypothyroidism in the latter screening. From the results obtained through our investigation of the thyroid function of these 9 infants, we confirmed that mild hypothyroidism can be better detected by the screening of TSH. (2) As to the program of the screening, we chose from the latter half of our screening all the samples in which TSH concentrations contained above 3 percent of each assay and were remeasured on the next assay. (3) As we confirmed that the sensitivity of measurement was increased at very low concentrations, when the volume of antibodies, radioisotopes and eluates used for each assay were decreased, we measured TSH successfully using two 3 mm discs. (4) As we can perform very simple screening by the 3 mm disc method, we are changing the screening method from that with 10 mm disc to one with two 3 mm discs. We intend to extend our screening, and will make every effort to prevent mental retardation due to congenital hypothyroidism.

Blood Preservation↗