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Biomedical subjects

T Sugimura

Publications and source records attributed to T Sugimura.

At least 847 records · Page 47Linked to original sources

Formation of mutagens in cooked foods. III. Isolation of a potent mutagen from beef.

The major mutagenic component of fried beef has been isolated using a series of chromatographic steps. The pure compound has been analyzed by low and high resolution mass spectroscopy and nuclear magnetic resonance spectroscopy. The results indicate that the molecular weight of this extremely mutagenic compound is 198, with an elemental composition of C11H10N4. The compound is different from the known mutagenic pyrolysis products of amino acids or proteins.

Animals↗

Detection of potent mutagens, Trp-P-1 and Trp-P-2, in broiled fish.

The potent mutagens Trp-P-1 (3-amino-1, 4-dimethyl-5H-pyrido-[4,3-b]-indole) and Trp-P-2 (3-amino-1-methyl-5H-pyrido[4,3-b]indole) are known to be produced by pyrolysis of tryptophan [8]. To determine whether such mutagens are produced by cooking foods, the fractions obtained from broiled sardines cooked in the ordinary way were analysed by gas chromatography/mass spectrometry. The results showed that 13.3 ng of Trp-P-1 and 13.1 ng of Trp-P-2 were, in fact, present per gram of broiled sardines.

Animals↗

Induction of differentiation of human and murine myeloid leukemia cells in culture by tunicamycin.

Tunicamycin, an antibiotic that specifically blocks the synthesis of N-acetylglucosamine-lipid intermediates and thereby prevents glycosylation of glycoproteins, induced differentiation of both human (HL-60) and murine (M1) myeloid leukemia cell lines in culture. At 0.1-1.0 microgram/ml, it induced differentiation of both HL-60 and M1 cells, characterized by increase in phagocytic cells and changes to resemble mature myeloid cells. Fc receptors were also induced in M1 but not in HL-60 cells; induction of intracellular lysozyme activity was not detected in either HL-60 or M1 cells. With this concentration of tunicamycin, there was marked decrease in rate of incorporation of radioactive glucosamine into macromolecules and a decrease in the rate of DNA synthesis. These data show that glycosylation of cellular proteins has an important role in maintaining these myeloid leukemia cells in an undifferentiated state in culture. The results also indicate that induction of phagocytosis in both HL-60 and M1 myeloid leukemia cells and of Fc receptors in M1 cells does not require continued synthesis of the oligosaccharide portions of cellular proteins by the lipid-linked pathway.

Cell Differentiation↗

Absence of albumin mRNA in the liver of analbuminemic rats.

Albumin synthesis in the liver of analbuminemic rats, established as a strain from a stock of Sprague-Dawley rats, was examined in vivo by labeling protein by intraperitoneal injection of L-[3H]leucine. Albumin was not synthesized in the liver of analbuminemic rats, whereas its synthesis amounted to about 14% of the total protein synthesis in the liver of normal rats. The RNA content and size distribution of the total polysomes in the liver of analbuminemic rats were not significantly different from those of normal rats. However, no functional mRNA coding for albumin was found in poly(A)-containing RNA from the liver of analbuminemic rats when tested with a cell-free translation system derived from rabbit reticulocytes. Moreover, the amount of the RNA sequence that could hybridize to purified albumin cDNA was more than 750 times greater in the liver of normal rats than in that of analbuminemic rats.

Animals↗

Effect of methyl substitution on mutagenicity of 2-aminodipyrido.

The mutagenicities of 2-aminodipyrido [1,2-a:3',2'-d] imidazole (Glu-P-2, a mutagen obtained from pyrolysate of glutamic acid) and six methyl substituted derivatives of Glu-P-2 were tested with Salmonella typhimurium TA98 and TA100 with S-9 mix. Glu-P-1 (6-Me-Glu-P-2) was the strongest mutagen to TA98 and TA100. 3-Me-Glu-P-2 was weakest. The presence of a methyl group, and its position were shown to affect the mutagenicity significantly.

Imidazoles↗

Purification and characterization of pepsinogens and a unique pepsin from rat stomach.

Four pepsinogens (1, 2, 3 and 4) (zymogens of pepsin A, EC 3.4.23.1, or pepsin C, EC 3.4.23.3) were purified from the fundic mucosa of rat stomach to homogeneous states as judged by sodium dodecyl sulfate/polyacrylamide gel electrophoresis and a unique pepsin was purified from pepsinogen 1. The molecular weights of pepsinogens 1, 2, 3 and 4 were 42 000, 40 000, 40 500 and 39 000, respectively, and those of the respective activated pepsins (1, 2, 3 and 4) were 35 500, 40 000, 35 500 and 37 000, respectively, as estimated by polyacrylamide gel electrophoresis. The amino acid compositions of these four zymogens differed, but resembled those of pepsinogen Cs from various animal species. Rabbit antiserum prepared against pepsinogen 1 reacted with pepsinogen 2, but not with pepsinogens 3 or 4. The precipitin line against pepsinogen 1 fused completely with that against pepsinogen 2. Purified pepsin 1 was a unique pepsin showing remarkable stability in alkali. It resembled pepsin A with respect to inhibition by pepstatin and pepsin C with respect to its amino acid composition, but had properties intermediate between those of pepsin A and C with respect to its optimal pH (2.1 to 3.1) with hemoglobin and activity on N-acetyl-L-phenylalanyl-L-diiodotyrosine.

Amino Acids↗

Distribution of marker enzymes and mucin in intestinal metaplasia in human stomach and relation to complete and incomplete types of intestinal metaplasia to minute gastric carcinomas.

Intestinal metaplasia of the human stomach was classified into two types, complete and incomplete. The complete type was associated with the intestinal marker enzymes sucrose alpha-D-glucohydrolase, alpha, alpha-trehalase, aminopeptidase (microsomal) (APM), and alkaline phosphatase (ALP). Tissue of this type contained goblet cells and Paneth's cells but not high-iron diamine (HID)-positive mucin staining with HID-Alcian blue. The incomplete type of intestinal metaplasia was associated with sucrose alpha-D-glucohydrolase, APM, goblet cells, and HID-positive mucin but not with alpha, alpha-trehalase, ALP, or Paneth's cells. For the examination of the distribution of the complete and incomplete types in 84, 27, and 16 resected specimens of human stomach with gastric carcinoma, gastric ulcer, and duodenal ulcer, respectively, disaccharidases were located with Tes-Tape. Specimens with intestinal metaplasia were divided into three classes: complete type only (class I), incomplete type only (class II), and a mixture of areas of the complete and incomplete types (class III). Of the 84 specimens from patients with gastric carcinoma, intestinal metaplasia was found in 76 (01%), and the percentages of specimens of classes I, II, and III were 32, 22, and 46, respectively. In these specimens, the percent incidence of class I increased and that of class II decreased with age. Of the 27 specimens from patients with gastric ulcer, 16 (59%) shopwed intestinal metaplasia and 10 of the 16 (63%) specimens were of class II. Of the 16 specimens from patients with duodenal ulcer, only 3 (19%) specimens showed intestinal metaplasia and all of them were of class II. The relationships of the complete and incomplete types of intestinal metaplasia to gastric carcinoma wre studied in 26 foci of minute carcinoma of the stomach less than 5 mm in largest diameter. Nineteen of 20 (05%) foci of the intestinal type of minute carcinoma were surrounded by intestinal metaplasia and 16 foci (80%) were surrounded by the incomplete type of intestinal metaplasia.

Adult↗

Induction of liver tumors in Wistar rats by sodium nitrite given in pellet diet.

Sodium nitrate was given to male noninbred Wistar rats at levels of 800 ppm and 1,600 ppm in a pellet diet for 646 experimental days. The first tum or was found on day 441 in the liver of a rat given a diet containing 800 ppm sodium nitrite. On day 646, liver tumors were found in 1 of 22 rats (4.5%) on an 800-ppm sodium nitrite diet and in 5 of 19 rats (26.3%) on a 1,600-ppm sodium nitrite diet. The incidence of liver tumors in the rats fed 1,600 ppm sodium nitrite was significantly different from that in controls as judged by the t-test (P < 0.05). A hepatocellular carcinoma and a hemangioendothelial sarcoma of the liver were found on day 646 in 2 rats fed 1,600 ppm sodium nitrite. One mammary tumor but no liver tumors were found in the 19 control rats. The concentration of sodium nitrite decreased after preparation of the pellet diet, but it was still at least 70% of the initial amount when the pellets were given to the rats. Volatile N-nitroso compounds, especially dimehylnitrosamine, at ppm levels were detected in the pellet diet with a gas chromatography-thermal energy analyzer.

Adenoma↗

Increased agglutinability of bladder cells by concanavalin A after administration of carcinogens.

The agglutination by concanavalin A of isolated epithelial cells of the rat bladder was examined after in vivo treatment of rats with various bladder carcinogens for one week. The carcinogens tested were N-butyl-N-(4-hydroxybutyl)nitrosamine, dibutylnitrosamine, N-[4-(5-nitro-2-furyl)-2-thiazolyl]formamide, 2-acetylaminofluorene, 2-napthylamine, benzidine, N-methyl-N-nitrosourea, and cyclophosphamide, and they were given to male Wistar rats p.o., s.c., intravesically, or i.p. As negative controls, the effects of administration of 2-(2-furyl)-3-(5-nitro-2-furyl)acrylamide, dimethylnitrosamine, N-methyl-N'-nitro-N-nitrosoguanidine, and surgical implantation of glass beads in the bladder were also tested. One week after the start of treatment, epithelial cells were isolated from the bladder by sonication, and agglutination of the isolated cells with concanavalin A was assayed. The observed agglutinabilities of isolated cells were found to be closely correlated with the reported bladder carcinogenicities of these chemicals in rats. Thus, concanavalin A agglutination of bladder cells should be a useful rapid in vivo mammalian system for screening bladder carcinogens.

2-Acetylaminofluorene↗

Effect of simultaneous administration of leupeptin on induction of bladder tumors in rats by N-butyl-N-(4-hydroxybutyl)-nitrosamine.

Male Wistar rats were given a diet containing 0.1% leupeptin, a microbial protease inhibitor, and drinking water containing 0.01% N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN) for 8 weeks. Leupeptin did not have any detectable effect on the induction of bladder tumors by BBN in week 40, in terms of the weight of the bladder including the tumor, the number of tumors per bladder, the extent of invasion, or the incidences of hyperplasia, papilloma, and cancer. This result is in marked contrast to the previous findings that leupeptin enhanced BBN-induced bladder carcinogenesis when administered continuously after BBN-treatment.

Animals↗

Inhibition of experimental blood-borne lung metastasis by protease inhibitors.

The inhibitory effects of protease inhibitors on blood-borne metastasis in male Donryu rat lung were studied. Injection i.v. of 10(6) Yoshida ascites hepatoma AH7974 cells induced about 118 +/- 92 (S.D.) metastatic foci in rat lung after 3 weeks. Leupeptin (50 mg/kg body weight twice a day), injected i.p. from 2 days before to 4 days after the inoculation of tumor cells, reduced the number of metastatic foci to about 49 +/- 45 (p less than 0.005). Leupeptin also suppressed the formation of metastatic foci of Yoshida ascites hepatoma AH100B cells (p less than 0.001). Elastatinal (100 mg/kg body weight twice a day) and chymostatin (100 mg/kg body weight once a day) did not inhibit formation of metastatic foci of AH7974 cells. Injection i.v. of 10(6) AH7974 cells induced pulmonary thrombi within 1 hr. Leupeptin (50 mg/kg body weight twice a day) reduced the number of thrombi from 1298 +/- 395 to 646 +/- 218, when injected i.p. for 2 days before the inoculation of the cells (p less than 0.005). Chymostatin and elastatinal did not significantly change the number of pulmonary thrombi. These results indicate that leupeptin inhibited metastasis formation and suggest that this effect may be due to the inhibition of thrombus formation after the arrest of circulating tumor cells.

Animals↗

Chemotherapeutic study on canine gastric cancer induced by N-ethyl-N'-nitro-N-nitrosoguanidine.

Studies were made on the chemotherapy of gastric cancer in dogs induced by N-ethyl-N'-nitro-N-nitrosoguanidine (ENNG). Four male Beagle dogs were given a solution of ENNG at 100 approximately 150 microgram/ml with or without 0.4% Tween 60 to drink for 5 approximately 8 months. They all developed gastric adenocarcinomas, which were confirmed by histological examination of biopsy specimens taken in months 13 approximately 32 of the experiment. After confirming the presence of gastric cancer, 1-n-hexylcarbamoyl-5-fluorouracil (HCFU), a derivative of 5-fluorouracil, was given to the dogs orally as capsules at a daily dose of 5 or 10 mg/kg body weight. One dog died from adverse effects of HCFU 12 days after the beginning of chemotherapy. The other 3 dogs were treated with CHFU for 82 approximately 424 days. In these dogs, the tumor size, measured by X-ray examination, increased during chemotherapy. On autopsy, the tumors in the stomach were found to be restricted to the antrum, and metastases of the gastric adenocarcinomas to the regional lymph nodes and/or liver were found in 2 dogs. No degenerative changes of tumor cells were found in the stomach or metastasized organs, except for necrosis of cells in a perigastric regional lymph node of the dog. The value of using canine gastric cancer in studies on chemotherapy is discussed.

Adenocarcinoma↗