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Biomedical subjects

T Sugimura

Publications and source records attributed to T Sugimura.

At least 829 records · Page 46Linked to original sources
PubMed1980

Test of carcinogenicity of quercetin, a widely distributed mutagen in food.

The carcinogenicity of quercetin, a flavonol, was tested in six-week-old ddY mice of both sexes. Groups of 38 males and 35 females were given pellet diet containing 2% quercetin throughout their life span. As controls, 16 males and 15 females were given basal diet. Animals in both test and control groups developed leukemia and tumors of the lung, forestomach, mammary gland, adrenal, and soft part tissues. In addition, some animals in groups treated with quercetin developed tumors of the heart, liver, salivary gland, ovary, and uterus. The incidences of these tumors in test and control groups were not statistically different.

Animals↗
PubMed1980

Sequential studies on the histopathogenesis of gastric carcinoma in rats by a weak gastric carcinogen, N-propyl-N'-nitro-N-nitrosoguanidine.

Sequential studies were made on the histopathologic changes in the glandular stomach of rats induced by a weak carcinogen. N-propyl-N'-nitro-N-nitrosoguanidine (PNNG). Fiftyfour rats were given 100 micrograms/ml of PNNG in their drinking water for 44 weeks, and then normal tap water until the end of the experiment. Rats were killed at intervals between week 1 and week 88. No marked atrophy or ulceration of the mucosa was found between week 1 and the end of the experiment. Focal intestinal metaplasia was found in week 19 and its incidence increased during the experiment. Adenocarcinoma in situ with extreme cellular atypia was found in mucosa with a normal appearance in week 67. An adenocarcinoma invading the submucosa was found in week 69, and one invading the serosa in week 88. All these pathological lesions were found on the anal side of the pyloric region. No pathologic changes were found in the fundic region. The sequential changes of the mucosa of the glandular stomach induced by this weak gastric carcinogen, PNNG, were very different from those induced by the potent gastric carcinogen, N-methyl-N'-nitro-N-nitrosoguanidine (MNNG). Gastric carcinoma induced by PNNG seems to be more similar to human gastric cancer than that induced by MNNG.

Adenocarcinoma↗
PubMed1980

Relationship between ornithine decarboxylase-inducing activity and configuration at C-4 in phorbol ester derivatives.

Measurements were made of induction of ornithine decarboxylase activity after painting mouse skin with 12-O-hexadecanoyl-16-hydroxyphorbol-13-acetate and its two epimeric 4-deoxy-analogs, 12-O-hexadecanoyl-4-deoxy-16-hydroxyphorbol-13-acetate and 12-O-hexadecanoyl-4-deoxy-4 alpha-16-hydroxyphorbol-13 acetate. The inductive activities of HHPA and 4-deoxy-HHPA were similar, but 4-deoxy-4 alpha HHPA had no inductive activity. These findings on natural phorbol esters confirm that both the 4 beta-hydrogen and the 4 beta-hydroxyl in phorbol esters are essential for ODC-inducing activity. The interactions of 4-deoxy-HHPA and 4-deoxy-4 alpha-HHPA with a possible receptor are discussed.

Animals↗
PubMed1980

Isolation of a recombinant influenza virus (Hsw 1 N2) from swine in Japan.

Outbreaks of swine influenza were first observed in Japan in 1978. A number of influenza viruses were isolated from diseased swine. Almost all viruses isolated were swine influenza virus (Hsw 1 N1) but two viruses isolated from the nasal swabs of swine showing clinical signs of influenza in the Kanagawa prefecture were characterized antigenically as Hsw 1 N2. Analysis of swine sera showed that influenza virus Hsw 1 N2 was epidemic in the farm from which the virus had been isolated. The new virus (Hsw 1 N2) seems to have been produced by recombination between swine influenza virus (Hsw 1 N1) and Hong Kong influenza virus (H3N2).

Animals↗
PubMed1980

Intracerebral pathogenicity of influenza A viruses for chickens.

The virulence of influenza A viruses was determined using the intracerebral pathogenicity index test for chickens. The viruses were divided into high virulent, low virulent and avirulent strains. A low virulent strain was recovered from the jejunum and faeces of infected chickens.

Animals↗
PubMed1980

Myeloperoxidase-catalyzed binding of 3-amino-1-methyl-5H-pyrido[4,3-b]indole, a tryptophan pyrolysis product, to protein.

Incorporation of 3-amino-1-methyl-5H-pyrido[4,3-b]indole (Trp-P-2), the principal mutagen in a tryptophan pyrolysate, into bovine serum albumin was catalyzed by myeloperoxidase. Hydrogen peroxide was essential for the incorporation reaction and albumin was required for optimal incorporation of Trp-P-2 into protein. Other various proteins, such as histone, lysozyme, cytochrome c, and gamma-globulin could also incorporate Trp-P-2, but poly(L-Arg), poly(L-Lys), and poly(L-Glu) could not. The incorporation of Trp-P-2 into albumin was inhibited by L-tyrosine and L-tryptophan, but not by other amino acids. Trp-P-2 incorporated into albumin was not released from the protein by treatment with 0.3 N HCl, or 0.3 N NaOH for 2 h at 35 degrees C, or with 1% sodium dodecylsulfate for 2.5 min at 100 degrees C. On electrophoresis on polyacrylamide containing sodium dodecylsulfate or urea and on chromatography on Sepharose CL-6B in 6 M guanidine/HCl, Trp-P-2 incorporated into albumin or lysozyme migrated with these proteins. These findings indicate that Trp-P-2 is covalently bound to these acceptor proteins.

Albumins↗
PubMed1980

Inhibition by norharman of metabolism of benzo[a]pyrene by the microsomal mixed function oxidase of rat liver.

The effect of norharman on the metabolism of ethyl acetate-soluble metabolic intermediates of benzo[a]pyrene (BP), 9,10-dihydro-9,10-dihydroxybenzo[a]pyrene (9,10-diol), 4,5-dihydro-4,5-dihydroxybenzo[a]pyrene (4,5-diol), 7,8-dihydro-7,8-dihydroxybenzo[a]pyrene (7,8-diol), benzo[a]pyrene diones, 3-hydroxybenzo[a]pyrene (3-OH-BP) and 9-hydroxybenzo[a]pyrene (9-OH-BP), were studied. These metabolic intermediates were converted by microsomal enzymes to other more polar ethyl acetate-soluble metabolites and then finally to the water-soluble metabolites. Norharman inhibited markedly the disappearance of each metabolite added as a substrate. With high-pressure liquid chromatographic (HPLC) separation it was revealed that formation of more polar metabolite was more efficiently inhibited by norharman than the formation of less polar metabolite. Formation of water-soluble metabolite was most efficiently inhibited by norharman. The mechanisms of the inhibitory effect of norharman on BP metabolism were studied by difference spectroscopy. On the addition of norharman, microsomes showed a type II difference spectrum, while on the addition of BP, they showed a type I difference spectrum. 3-OH-BP and 4,5-diol also gave a type I spectrum. Thus both BP and its metabolites bind to the active center of P-450, whereas norharman binds to the sixth ligand position of the iron ion of P-450. Kinetic studies showed that the Km-value of microsomes for BP was 6.25 microM in the presence and absence of norharman. This indicated that norharman inhibits the metabolism of BP non-competitively.

Alkaloids↗
PubMed1980

Isolation and characterization of active metabolites of tryptophan-pyrolysate mutagen, TRP-P-2, formed by rat liver microsomes.

The mutagenic compound derived from the pyrolysis of tryptophan, 3-amino-1-methyl-5H-pyrido-[4,3b]indole (Trp-P-2) was metabolized by rat liver microsomes to more than four metabolites, separable by high performance liquid chromatography. Among these metabolites, two metabolites, M-3 and M-4 were directly active in increasing the frequency of mutation in Salmonella typhimurium TA98. Treatments of rats with polychlorinated biphenyl (PCB) or 3-methylcholanthrene dramatically induced the activity of liver microsomes to form these active metabolites, while treatment with phenobarbital was without effect. A major active metabolite (M-3) formed the pentacyano-ammine ferroate, which is known to be formed by reaction of sodium pentacyano-ammine ferroate with some hydroxylamines. Further this metabolite was oxidized to the minor active metabolite (M-4) with potassium ferricyanide or gamma-manganese dioxide, and was reduced back to Trp-P-2 with titanium trichloride. These results indicated that the major active metabolite of Trp-P-2, which is formed by cytochrome P-450, is the 3-hydroxyamino derivative.

Animals↗
PubMed1980

Enhancement of the mutagenicities of N-methyl-N'-nitro-N-nitrosoguanidine and N-methyl-N-nitrosourea by glucose.

The mutagenicity of N-methyl-N'-nitro-N-nitrosoguanidine to Salmonella typhimurium hisG46 was enhanced by pre-incubating the chemical with bacteria in sodium phosphate buffer. Addition of glucose (to 15 mM) to the pre-incubation mixture further enhanced the mutagenicity. Pre-incubation with glucose also increased the mutagenicity of N-methyl-N-nitrosourea. Fructose, galactose, pyruvate and succinate also enhanced the mutagenicity of N-methyl-N'-nitro-N-nitrosoguanidine. The effect of glucose was observed with S. typhimurium strains hisG46, TA1975, TA1950, TA1535 and TA100.

Biotransformation↗
PubMed1980

Inactivation of mutagens from pyrolysates of tryptophan and glutamic acid by nitrite in acidic solution.

The mutagenic aromatic amines Trp-P-1, Trp-P-2 and Glu-P-1, isolated frm pyrolysates of tryptophan and glutamic acid, at the concentration of 0.025 mM were treated with 0.05 mM nitrite at various pH values at 37 degrees C. The resulting reaction mixtures were tested for mutagenicity towards Salmonella typhimurium TA98 and TA100. When treated with nitrite at this physiologically realistic concentration, these mutagenic aromatic amines were readily converted to extremely weak or non-mutagenic deaminated compounds. These deaminated products were identified as the corresponding hydroxy compounds by mass and proton magnetic resonance spectroscopies. Comparative kinetic studies were made on the disappearance of the mutagenic aromatic amines. The half-life (t1/2 of Glu-P-1 on treatment with nitrite at pH 1.6 was less than 5 min, and those of Trp-P-1 and Trp-P-2 were 95 and 105 min, resp.

Amines↗
PubMed1980

Mutagenicity of smoke condensates from joss sticks.

Smoke condensates obtained from 8 Japanese brands of joss sticks were assayed for mutagenicity on Salmonella typhimurium TA100 and TA98 with and without metabolic activation by S9 mix. An average of 22 mg of smoke condensate was obtained per joss stick weighing about 0.3 g. Smoke condensates obtained from all the joss sticks tested showed definite mutagenicity with a linear dose response on both tester strains of bacteria with metabolic activation. Without S9 mix, the smoke condensates from some of the joss sticks also showed positive mutagenicity on TA100 at 0.15 or 0.3 mg/plate. The revertant numbers over the background counts induced by 1-mg samples of the smoke condensates from joss sticks with S9 mix were 140--310 with TA100 and 90--200 with TA98. These values were one-fifth to half that of cigarette smoke condensate with TA100 and one-fourteenth to one-fifth that with TA98. However, it was calculated that, when joss sticks are burnt continuously in a closed space under the usual conditions, the mutagenicity of their smoke per unit volume of air is similar to that of the smoke produced by the smoking of two cigarettes per hour. Extracts of unburnt joss sticks with methanol, chloroform or dimethylsulfoxide had no mutagenicity, showing that the burning process produces the mutagenic substance(s).

Genetic Techniques↗
PubMed1980

Induction of sister-chromatid exchanges by mutagens from amino acid and protein pyrolysates.

Sister-chromatid exchanges (SCEs) in a permanent cell line of human lymphoblastoid cells were induced by 3-amino-1,4-dimethyl-5H-pyrido[4,3-b]-indole (Trp-P-1), 3-amino-1-methyl-5H-pyrido[4,3-b]indole (Trp-P-2), 2-amino-6-methyldipyrido[1,2-a:3',2'-d]imidazole (Glu-P-1) and 2-amino-9H-pyrido[2,3-b]indole (2-amino-alpha-carboline). The first two compounds were found in tryptophan pyrolysates, the third in a glutamic acid pyrolysate and the last in a globulin pyrolysate. All these compounds required the metabolic activation system (S9 mix) for induction of SCE. Trp-P-2 had the highest SCE-inducing activity of these chemicals (approximately equivalent to that of aflatoxin B1), followed by Trp-P-1, Glu-P-1 and then 2-amino-alpha-carboline.

Carbolines↗