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Biomedical subjects

T Sugimura

Publications and source records attributed to T Sugimura.

At least 703 records · Page 39Linked to original sources
PubMed1984

A new type of N-nitrosamino acid, N-nitroso-L-thioproline and N-nitroso-L-methylthioprolines, found in human urine as major N-nitroso compounds.

In addition to N-nitrosoproline (NPRO), N-nitrosamino acids of a new type containing sulfur were found as major N-nitroso compounds in the urine of seven healthy subjects. These compounds were detected using a gas chromatograph connected with a Thermal Energy Analyzer (GC-TEA), and they were identified as N-nitroso-L-thiazolidine-4-carboxylic acid (N-nitroso-L-thioproline, NTPRO) and the cis and trans isomers of N-nitroso-L-methylthiazolidine-4-carboylic acid (N-nitroso-L-methylthioproline, NMTPRO) by using gas chromatography-mass spectrometry (GC-MS). The amounts of NPRO, NTPRO and NMTPRO found in 100 mL samples of human urine were 65-471 ng, 67-2 250 ng and 275-5 825 ng, respectively. L-Thioproline was nitrosated 20-60 times faster than L-proline by nitrite over the whole range of acidic pH. The precursors of these new-N-nitrosamino acids containing sulfur may be formed by the reaction of L-cysteine with formaldehyde and acetaldehyde in the human body. These sulfur-containing N-nitroso compounds, NTPRO and NMTPRO, in addition to NPRO, could be useful as probes for investigation the dynamics of nitrosation in the human body.

Chromatography, Gas↗
PubMed1984

Multiple primary cancers in 5,456 autopsy cases in the National Cancer Center of Japan.

Multiple primary malignant neoplasms in 5,456 consecutive autopsy cases from 1962 to 1981 in the National Cancer Center were analyzed. There were 285 (5.2%) double primary cancers, 58 (1.1%) triple or more, and 65 (1.2%) minute cancers of the thyroid or prostate gland. Higher incidence of second cancer is observed in cancers of the oropharynx, intestine, larynx, uterus, bladder, and thyroid. Organ association between the two cancers was present in certain organs; for example, there was a tendency for upper gastrointestinal tract cancers to be associated with lower gastrointestinal tract cancers. Influence of histologic subtypes in multiple cancer cases is discussed for lung cancer.

Adult↗
PubMed1984

Structure-activity studies on synthetic analogues (indolactams) of the tumor promoter teleocidin.

Synthetic analogues (indolactams) related to the tumor promoter teleocidin were synthesized chemically. Of four indolactam-Vs lacking the monoterpenoid moiety of native teleocidin, (-)-indolactam-V bound to the 12-O-tetradecanoylphorbol-13-acetate receptor in cell membranes and induced both adhesion of HL-60 cells and ornithine decarboxylase activity in mouse skin, although its effects were weaker than those of teleocidin. (+)-Indolactam-V and two isomers of epi-indolactam-V showed no induction of ornithine decarboxylase. These results indicate that the S,S configuration of native teleocidin at the isopropyl residue and the hydroxymethyl group is necessary for activity.

Animals↗
PubMed1984

Interaction between quercetin and Ca2+-calmodulin complex: possible mechanism for anti-tumor-promoting action of the flavonoid.

Quercetin was found to have similar inhibitory effects on tumor promoter-induced phenomena to those of N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide, a calmodulin antagonist. Moreover, quercetin was shown to interact directly with the Ca2+-calmodulin complex. These results suggest that quercetin may act as a calmodulin antagonist, and that its antagonistic effect on calmodulin may be important in its anti-tumor-promoting action in vivo.

Animals↗
PubMed1983

Bromine residue at hydrophilic region influences biological activity of aplysiatoxin, a tumor promoter.

Aplysiatoxin and debromoaplysiatoxin, which are isolated from the seaweed, Lyngbya gracilis, differ in their chemical structure only by the presence or absence of a bromine residue in the hydrophilic region. The function and the structure-activity relation of the hydrophilic region are not known. Aplysiatoxin increased malignant transformation, stimulated DNA synthesis, and inhibited the binding of phorbol-12,13-dibutyrate and epidermal growth factor to cell receptors. Debromoaplysiatoxin inhibited the binding of these two substances as strongly as aplysiatoxin but did not increase malignant transformation or stimulate DNA synthesis. These results indicate that a slight change in the chemical structure of the hydrophilic region of aplysiatoxin affects its abilities to increase cell transformation and stimulate DNA synthesis and that the abilities of the tumor promoters to inhibit the binding of phorbol-12,13-dibutyrate and epidermal growth factor are dissociable from their abilities to increase cell transformation and stimulate DNA synthesis under some circumstances.

Animals↗
PubMed1983

Ultimate forms of mutagenic and carcinogenic heterocyclic amines produced by pyrolysis.

A mutant strain of Salmonella typhimurium TA98/1,8-DNP6 isolated by McCoy et al. (1) was reported to be defective in esterifying activity. We have found that 2-amino-6-methyldipyrido[1,2-a:3',2'-d]imidazole (Glu-P-1), 2-aminodipyrido[1,2-a:3',2'-d]imidazole (Glu-P-2), 2-amino-3-methylimidazo-[4,5-f]quinoline (IQ), 2-amino-3,4-dimethylimidazo[4,5-f]quinoline (MeIQ) and 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) were not mutagenic to TA98/1,8-DNP6 with S9 mix, while these compounds were strongly mutagenic to the original TA98 with S9 mix. The mutagenicities of some of these heterocyclic amines to TA98 were inhibited by pentachlorophenol, an aryl sulfotransferase inhibitor. These results indicate that the ultimate forms of these heterocyclic amines are probably sulfate esters of heterocyclic amine N-hydroxides. Contrary to this, 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-9H-pyrido[2,3-b]indole (A alpha C) and 2-amino-3-methyl-9H-pyrido[2,3-b]indole (MeA alpha C) were definitely mutagenic to TA98/1,8-DNP6, although less than to TA98.

Amines↗
PubMed1983

Relationship between histone H1 poly(adenosine diphosphate ribosylation) and histone H1 phosphorylation using anti-poly(adenosine diphosphate ribose) antibody.

The chromatin-associated enzyme poly(ADP-Rib) polymerase catalyzes the posttranslational modification of histones. Antibody to poly(ADP-Rib) has been coupled to Sepharose, and the resultant immunoadsorbent was used to fractionate, specifically, histone H1 subpopulations undergoing this nuclear protein modification. When this method of separation was used, it was additionally observed that poly-(ADP-ribosylated) H1 species were highly accessible to in vitro phosphorylation by nuclear protein kinase. Phosphorylated H1 molecules were retained by the anti-poly(ADP-Rib)-Sepharose column due to the presence of endogenous poly-(ADP-Rib) components. Degradation of the latter moieties on phosphorylated H1 reversed their adsorption to the column.

Adenosine Triphosphate↗
PubMed1983

Size and shape of poly(ADP-ribose): examination by gel filtration, gel electrophoresis and electron microscopy.

Digestion of the poly(ADP-ribose) with snake venom phosphodiesterase yielded phosphoribosyl-AMP and AMP in a ratio of 30 to 1, indicating the "chain length" of 30 if the poly(ADP-ribose) is a linear molecule as previously supposed. Gel filtration and gel electrophoresis, however, revealed a very heterogeneous size distribution, the average size being, much longer than (ADP-ribose)30. Electron microscopy of poly(ADP-ribose) showed an irregularly branched figure. Molecules with more than ten branched portions were observed. These results are in agreement with the recent identification of the chemical structure of the branched portion in poly(ADP-ribose).

Animals↗
PubMed1983

Activation of the EBV-cycle and aggregation of human blood lymphocytes by the tumor promoters teleocidin, lyngbyatoxin A, aplysiatoxin and debromoaplysiatoxin.

A variety of tumor promoters such as the phorbol esters were found to be capable of inducing the viral cycle in cell lines latently infected with Epstein-Barr virus (EBV). We tested two classes of new tumor promoters; indole alkaloids and polyacetates, for their ability to induce the synthesis of the Epstein-Barr virus determined early antigen (EA) complex. Teleocidin and lyngbyatoxin A are indole alkaloids. Aplysiatoxin and debromoaplysiatoxin are polyacetates. Of these four tumor promoters all but debromoaplysiatoxin induced the synthesis of the EA complex. However, in combination with 3 mM n-butyrate, all four induced EA synthesis. The potent tumor promoters teleocidin, lyngbyatoxin A and aplysiatoxin induced maximal synthesis of EA at the concentration of 5 to 10 ng/ml, whereas the weak tumor promoter debromoaplysiatoxin required a concentration of 250 ng/ml to achieve maximal induction. Phorbol esters induce quick morphological changes and aggregation of human blood lymphocytes. The latter phenomenon has been interpreted as the expression of a "cell binding phenotype" (Patarroyo et al., in press). We showed that all four promoters induced aggregation of human lymphocytes at similar concentrations. The induction seemed to be a common effect which could be induced by both strong and weak tumor promoters.

Alkaloids↗
PubMed1983

Increased agglutinability of bladder epithelial cells by concanavalin A in rats fed several biphenyl derivatives.

Biphenyl and its derivatives, 2-aminobiphenyl, 2-nitrobiphenyl, 4-aminobiphenyl, 4-nitrobiphenyl, p-phenylphenol, o-phenylphenol (OPP), and o-phenylphenol sodium salt tetrahydrate (OPP-Na) were examined for their bladder carcinogenicity in rats by a short-term assay for agglutinability of bladder epithelial cells with concanavalin A. Increased agglutinability was observed after 1-week treatment with 2.0% and 1.0% OPP, 2.0% and 1.0% OPP-Na, 0.5 and 0.1% 4-aminobiphenyl, and 0.5% 4-nitrobiphenyl in the diet, suggesting carcinogenicity of these compounds in the bladder. Such an increase in agglutinability was not observed in rats fed diets containing biphenyl, 2-aminobiphenyl, 2-nitrobiphenyl or p-phenylphenol at 2.0%. With OPP-Na, an in vivo carcinogenesis experiment was performed. Bladder carcinomas developed in 14 of 36 male Fisher rats fed a 2% OPP-Na diet for 50 weeks.

Agglutination Tests↗
PubMed1983

Teleocidin-induced modulation of growth and cell interaction in microenvironment-dependent mouse leukemias.

Teleocidin is a new tumor-promoting substance chemically unrelated to phorbol groups. Its biological effects on thymic microenvironment-dependent leukemias derived from AKR spontaneous leukemias were studied in vitro in comparison with 12-O-tetradecanoylphorbol 13-acetate (TPA), a representative tumor promoter of the phorbol group. Teleocidin stimulated the in vitro growth of 21 out of 31 symbiotic cell lines in the absence of growth-supporting stromal cells. All the responders to teleocidin were responsive also to TPA and the degree of growth stimulation in each cell line was comparable. Both promoters could inhibit the symbiotic complex formation with thymic epithelial cells probably by affecting the cytoskeleton. All symbiotically cultured AKR leukemia cells expressed Thy-1.1 antigen, but their expression of Lyt-1.2 and Lyt-2.1 was heterogenous. There was no direct correlation between teleocidin-responsiveness and Lyt-phenotypes of the leukemia cells.

Alkaloids↗
PubMed1983

Roasting coffee beans produces compounds that induce prophage lambda in E. coli and are mutagenic in E. coli and S. typhimurium.

Freshly brewed blended coffee, instant coffee and instant caffeine-free coffee induced prophage lambda in lysogenic E. coli K12, strain GY5027. Because coffee prepared from green beans by the same extraction method as used for freshly brewed blended coffee had no prophage-inducing activity, this activity may be attributed to compounds produced in the roasting process. Roasting also produced compounds that were mutagenic in S. typhimurium TA100 and E. coli WP2 uvrA/pKM101.

Bacteriophage lambda↗
PubMed1983

Mutagenic activity of heterocyclic amines in Chinese hamster lung cells with diphtheria toxin resistance as a marker.

The mutagenicities of 8 heterocyclic amines, which had been purified from pyrolysates of amino acids and proteins, broiled fish and fried beef, were assayed in Chinese hamster lung cells (CHL cells) in culture in the presence and absence of a metabolic activation system, with diphtheria toxin resistance as a selective marker. 3-Amino-1-methyl-5H-pyrido[4,3-b]indole (Trp-P-2) was the most mutagenic of the heterocyclic amines tested. 3-Amino-1,4-dimethyl-5H-pyrido[4,3-b]indole (Trp-P-1), 2-amino-3,4-dimethylimidazo[4,5-f]quinoline (MeIQ), 2-amino-3-methylimidazo[4,5-f]quinoline (IQ), 2-amino-9H-pyrido[2,3-b]indole (A alpha C), 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx), 2-amino-6-methyldipyrido[1,2-a:3',2'-d]imidazole (Glu-P-1) and 2-aminodipyrido[1,2-a:3',2'-d]imidazole (Glu-P-2) showed mutagenic activity on CHL cells, their specific activities being in the order shown above. All the compounds except Trp-P-1 required the presence of a metabolic activation system for mutagenicity on CHL cells.

Amines↗
PubMed1983

Inactivation of potent pyrolysate mutagens by chlorinated tap water.

The potent mutagens 3-amino-1-methyl-5H-pyrido[4,3-b]indole (Trp-P-2, 62450-07-1), 2-amino-6-methyldipyrido-[1,2-a:3', 2'-d]imidazole (Glu-P-1, 67730-11-4) and 2-amino-3-methylimidazo[4,5-f]quinoline (IQ, 76180-96-6), isolated from pyrolysates of tryptophan and glutamic acid and from broiled sardines, respectively, were effectively degraded by chlorinated tap water with a concomitant loss of mutagenicity toward Salmonella typhimurium TA98 and TA100. The half-life of 10 microM IQ in the presence of 1.5 ppm of residual chlorine was less than 10 sec; those of Glu-P-1 and Trp-P-2 were 0.5-1 and 2-3 min, respectively. This means that a glass of chlorinated tap water (150 ml) containing 1.5 ppm of residual chlorine can break down about 200 micrograms of these pyrolysate mutagens within a couple of minutes.

Carbolines↗
PubMed1983

Effect of poly(ADP-ribose)polymerase inhibitors on the frequency of sister-chromatid exchanges in Bloom syndrome cells.

The effect of inhibitors of poly(ADP-ribose)polymerase, benzamide (Bam) and m-aminobenzamide (m-AB), on sister-chromatid exchanges (SCEs) and cell growth, was examined in lymphoblastoid cell lines from a normal adult (KS-64) and from a Bloom syndrome patient (BS1-2). The presence of Bam and m-AB increased the levels of SCEs in KS-64 and BS1-2 lymphoblastoid cells. Though the net increase was similar in the two types of cell, the relative increase was much lower in the BS1-2 cells. Bam and m-AB increased the number of SCEs in BS1-2 cells to levels of 95.4 +/- 3.24 and 98.1 +/- 3.23 per cell, respectively, as compared with the baseline level of 75.5 +/- 2.16. On the other hand, when KS-64 cells were treated with Bam and m-AB, the number of SCEs increased to 27.1 +/- 1.98 and 28.6 +/- 2.71 per cell, respectively, compared with the baseline number of 6.7 +/- 0.41 per cell. These inhibitors of poly(ADP-ribose)polymerase also inhibited cell growth at concentrations which induced SCEs in KS-64 as well as in BS1-2 cells. No significant decrease in the poly(ADP-ribose)polymerase activity or in the amount of poly-(ADP-ribose) was detected in BS1-2 cells as compared with KS-64 cells. The mechanism by which SCEs are increased in BS1-2 cells is discussed.

Benzamides↗
PubMed1983

Role of flavonoids in suppressing the enhancement of phospholipid metabolism by tumor promoters.

Quercetin, a ubiquitous flavonoid in plants, inhibited the incorporation of [32P]inorganic phosphate (32Pi) into phospholipid of HeLa cells enhanced by 12-O-tetradecanoylphorbol-13-acetate (TPA), a potent tumor promoter. Among the flavonoids tested, luteolin was the most effective in inhibiting the action of TPA. Studies on structure-activity relationships demonstrated that more hydroxylated flavones and flavonols had stronger inhibitory effects. Quercetin and luteolin also inhibited enhancement of 32Pi-incorporation into phospholipid by dihydroteleocidin B, another potent tumor promoter. The inhibitory effect of quercetin on the biological action of tumor promoters is interesting in relation to the non-carcinogenicity of this flavonoid in animals, in spite of its mutagenicity.

Drug Interactions↗
PubMed1983

Agglutination assay of bladder cells by Concanavalin A proved the high susceptibility of analbuminemic rats to bladder carcinogens.

The susceptibility of analbuminemic rats, a mutant strain of Sprague-Dawley rats, to bladder carcinogens was examined by testing the agglutinability of isolated bladder epithelial cells by Concanavalin A (Con A). One-week treatment with 0.001% N-butyl-N-(4-hydroxybutyl)nitrosamine (BHBN) in the drinking water or 0.01% N-(4-(5-nitro-2-furyl)-2-thiazolyl)-formamide (FANFT), 0.01% and 0.1% 4-aminobiphenyl, 0.1% 4-nitrobiphenyl, 0.1% benzidine, 0.1% 2-napthylamine or 5% sodium saccharin in the diet clearly induced high agglutinability of bladder cells of male analbuminemic rats but not Sprague-Dawley rats. These results suggest that male analbuminemic rats are very susceptible to bladder carcinogens in general and therefore will be very useful in screening tests for bladder carcinogens.

2-Naphthylamine↗