Search PubMed⌕ Search

Biomedical subjects

T Sugimura

Publications and source records attributed to T Sugimura.

At least 757 records · Page 42Linked to original sources

Presence of N-nitroso-L-thioproline and N-nitroso-L-methylthioprolines in human urine as major N-nitroso compounds.

Unknown N-nitroso compounds were found in human urine of healthy volunteers by gas chromatography-thermal energy analysis. These compounds were identified as N-nitroso-L-thioproline and cis- and trans-N-nitroso-L-methylthioprolines by gas chromatography-mass spectrometry. The precursors of these new N-nitroso compounds may be formed by the reactions of L-cysteine with formaldehyde and acetaldehyde in the human body.

Chromatography, Gas↗

Mutagenicity of nitropyrenes in Chinese hamster V79 cells.

The mutagenic effects of 1-nitropyrene, and 1,3- and 1,8-dinitropyrenes on Chinese hamster V79 cells in the presence or absence of X-irradiated Syrian hamster embryo cells were examined. Without Syrian hamster embryo cells, 1,3-dinitropyrene had weak mutagenic activity and 1,8-dinitropyrene had strong, dose-related mutagenic activity. With Syrian hamster embryo cells, the mutagenicities of both 1,3-and 1,8-dinitropyrenes were appreciably increased. 1-Nitropyrene did not induce ouabain-resistant mutants at concentrations of up to 10 micrograms/ml either with or without Syrian hamster embryo cells.

Animals↗

Restriction fragment length polymorphism of the rat albumin gene in Sprague-Dawley rats and its application in genetic study of analbuminemia.

Restriction fragment length polymorphism of the rat albumin gene was discovered in a stock of Sprague-Dawley rats by Southern blots of rat liver DNAs using cloned albumin cDNA, prAlb-1 (1), as a probe. The polymorphic DNA fragments were observed when rat DNAs were digested with either Hind III or Pst 1 and the difference in length of the DNA fragments in Hind III or Pst 1 digests was estimated as 1.4 kbp. When DNAs were digested with EcoR I, restriction fragment length polymorphism was not observed. Therefore, this polymorphic DNA was concluded to be located in the flanking sequence. Structural analysis of the cloned albumin gene showed that the polymorphism was located in the 3'-flanking sequence. With this polymorphism as a marker of the albumin structural gene, the phenotype of analbuminemia, which is an autosomally recessive trait, was found to be linked to the structural gene of albumin.

Animals↗

A new tumor-promoting agent, dihydroteleocidin B, markedly enhances chemically induced malignant cell transformation.

Teleocidin, which was isolated from mycelia of Streptomyces, is a potent tumor promoter in mouse skin. The catalytically hydrogenated compound dihydroteleocidin B markedly enhanced malignant cell transformation induced by 3-methylcholanthrene or ultraviolet radiation. Dihydroteleocidin B was at least 100 times more effective in enhancing transformation than 12-O-tetradecanoyl phorbol-13-acetate, the strongest promoter known until now, whereas both promoters showed equal capacities to induce early membrane effects and DNA synthesis.

Alkaloids↗

Induction of differentiation in human promyelocytic leukemia cells by tumor promoters.

12-)-Tetradecanoylphorbol-13-acetate (TPA), the prototype polyfunctional diterpene ester tumor promoter of two-step carcinogenesis in mouse skin, induced differentiation of human promyelocytic leukemia cells (HL-60) in culture. Differentiation of HL-60 cells was characterized by increased phagocytosis, increased lysozyme activity (EC 3.2.1.17) in the growth medium, and changes in morphology to those characteristics of more mature cells resembling macrophages. Many of the cells treated with TPA became aggregated, attaching firmly to culture flasks. The average intracellular myeloperoxidase activity (EC 1.11.1.7) per cell decreased during induction of differentiation by TPA. It was also found that TPA enhanced, rather than inhibited, differentiation of HL-60 cells induced by DMSO. In addition to TPA, several polyfunctional diterpene esters of the tigliane, ingenane, and daphnane type have been tested for their ability to induce morphological and functional changes of HL-60 cells. The activities of the compounds to induce these changes correlated well with their activities as tumor promoters in two-step carcinogenesis in mouse skin. In particular, half the concentrations required for induction of adhesion of the cells to flasks were roughly correlated to the potency of these compounds as tumor promoters. Among the compounds tested, phorbol-12,13-didecanoate (PDD), ingenol-3-hexadecanoate, Pimelea factor P1 and Pimelea factor P2 were as active as TPA, while 4-O-methyl-TPA and 4 alpha-PDD were much less active. Phorbol and ingenol were totally inactive up to a concentrations 10,000-fold higher than that of TPA.

Cell Adhesion↗

Sulfite suppresses the mutagenic property of coffee.

The mutagenicity of instant and freshly brewed coffee on Salmonella typhimurium TA100 and TA98 without S9 mix was inactivated by sodium sulfite. Sulfite ion at a dose of 200 ppm almost completely inactivated the mutagenicity of coffee made in the ordinary way (5-15 mg dry weight/ml). Sodium bisulfite and potassium metabisulfite had similar effects. On the contrary, L-ascorbic acid enhanced the mutagenicity of coffee. Sodium sulfite also inactivated the phage-inducing activity of coffee in inductest III. Sodium sulfite completely suppressed the mutagenicities of 1,2-dicarbonyls, namely diacetyl and glyoxal. Diacetyl is present in coffee, beer, butter and other foods and drinks. Because sodium sulfite, sodium bisulfite and potassium metabisulfite are widely used as food additives, they should be useful in reducing the levels of mutagens in foods.

Bacteriophage lambda↗

Comutagenic effect of norharman with aminopyridine derivatives.

The mutagenicities of 3 monoaminopyridines, 4 methyl-substituted monoaminopyridines and 3 diaminopyridines were tested with or without norharman in the Salmonella assay system. None of the compounds was mutagenic without norharman. However, 3-aminopyridine and 2-amino-3-methylpyridine were mutagenic in the presence of norharman and S9 mix; 3-aminopyridine was mutagenic to TA98, but not to TA100, while 2-amino-3-methylpyridine was mutagenic to both TA98 and TA100, although its mutagenicity was much stronger in TA98.

Alkaloids↗

Carcinogenicity in rats of the mutagenic compounds 1-nitropyrene and 3-nitrofluoranthene.

1-Nitropyrene and 3-nitrofluoranthene are present in diesel exhaust, in pollutants in air, and were also present in certain xerographic toners and copies. Their carcinogenicities were studied in male F344/DuCrj rats by subcutaneous injection. Sarcomas, mainly malignant fibrous histiocytomas at the site of injection were induced in 8 to 17 (47%) rats by 1-nitropyrene and in 4 of 10 (40%) rats by 3-nitrofluoranthene. Some tumors were serially transplantable in the same strain of rats.

Air Pollutants↗

Presence of albumin mRNA precursors in nuclei of analbuminemic rat liver lacking cytoplasmic albumin mRNA.

Analbuminemic rats, which lack serum albumin, were previously found to have no albumin mRNA in the cytoplasm of the liver. In the present study, the existence of nuclear albumin mRNA precursors in the liver of analbuminemic rats was examined by RNA X cDNA hybridization kinetics. Albumin mRNA precursors were present in the nuclei of analbuminemic rat liver at almost normal levels, despite the absence of albumin mRNA from the cytoplasm. Nuclear RNA of analbuminemic rat liver was subjected to electrophoresis on 1% agarose gel in parallel with nuclear RNA of normal rat liver. RNA was transferred from the gel to diazobenzyloxymethyl-paper and hybridized to cloned cDNA. Several bands of putative albumin mRNA precursors were obtained with nuclear RNA of analbuminemic rat liver and some of them were indistinguishable from those of normal rat liver. Nuclear RNA of analbuminemic rats was hybridized to 3'-end-labeled cloned cDNA under the conditions of RNA excess and then digested completely with S1 nuclease and subjected to electrophoresis on polyacrylamide gel. By this technique, nuclear RNA that could hybridized to cDNA was found to have the albumin mRNA sequence in at least the 3' half of the mRNa that was covered by cloned cDNA. For comparison of the structures of the albumin genes of analbuminemic and normal rats, DNAs from rat livers of both types were digested completely with EcoRI, HindIII, and Pst I; the fragments were separated by electrophoresis on 1% agarose gel, transferred to nitrocellulose paper, and hybridized to cloned cDNA. The intensities of the corresponding bands and the digestion patterns of the analbuminemic and normal rat genes were indistinguishable. From these data, it is concluded that analbuminemic rats have a unique type of mutation(s) affecting albumin mRNA maturation.

Animals↗

Carcinogenicity test of quercetin and rutin in golden hamsters by oral administration.

Quercetin and its glycoside, rutin were tested for carcinogenicity in non-inbred golden hamsters of both sexes. In Experiment I, 10% quercetin, 10% rutin, or control diet was given to animals for 735 days. In this experiment, tumors appeared mainly in the forestomach, but the incidence was not statistically different among the three groups. Quercetin and rutin were not carcinogenic under these conditions. In Experiment II, Group 1 was given 4% quercetin diet for 709 days. Group 2 was given 1% quercetin diet for 351 days and then the basal diet for 350 days. Group 3 was given 1% quercetin diet and then 1% croton oil diet and Group 4 was given the basal diet followed by 1% croton oil diet, for the same periods as Group 2. Group 5 was given the basal diet for 701 days. In Experiment II, papillomas of the forestomach appeared in Groups 1, 2, and 5, and papillomatosis in Group 3 and 4. There were no statistical differences among experimental groups and respective controls. Thus, quercetin was not carcinogenic when given at the concentrations of 4% and 1%; even with the administration of 1% croton oil after 1% quercetin, there was no increase in tumor incidence.

Administration, Oral↗

Teleocidin from Streptomyces is a potent promoter of mouse skin carcinogenesis.

Teleocidin, isolated from Streptomyces mediocidicus ISP 5021, is an indole alkaloid. The teleocidin used was composed of teleocidin A, teleocidin B and their isomers. A hydrogenated derivative of teleocidin B, dihydroteleocidin B, was recently reported to have tumor promoting activity in vivo and various biological activities in vitro, with a specific activity comparable to that of 12-O-tetradecanoylphorbol-13-acetate (TPA). This paper describes the potent tumor promoting activity of the parent compound of dihydroteleocidins, teleocidin, on mouse skin in two-stage carcinogenesis. The tumor promoting activity was evaluated by measuring the incidence and yield of tumors, and by histological examination. Groups of mice were given a single application of 100 micrograms of 7,12-dimethylbenz[a]anthracene (DMBA) and then 2.5 micrograms of teleocidin twice weekly or the same dose of DMBA plus 2.5 micrograms of TPA twice weekly. Both groups showed 100% tumor incidence after 24 weeks, and the tumor yields were 4.0 tumors per mouse in the former group and 9.8 per mouse in the latter group in week 30. We confirmed, through this experiment, that teleocidin is as potent as TPA in in vivo two-stage carcinogenesis in mouse skin. These two structurally unrelated classes, indole alkaloid and phorbol ester, showed tumor promoting activity in almost the same range.

9,10-Dimethyl-1,2-benzanthracene↗