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T Sugimura

Publications and source records attributed to T Sugimura.

At least 811 records · Page 45Linked to original sources

Carcinogenicity examination of quercetin and rutin in ACI rats.

Carcinogenicity of quercetin and rutin were examined in inbred ACI strain rats. Rats were given a diet containing 1% or 5% quercetin or 5% rutin for 540 days, or 10% quercetin and 10% rutin for 850 days. Rats in control groups were fed a normal basal diet. Most tumors found in experimental groups were also found in the corresponding control groups. Furthermore, there was no significant difference between the incidence of tumors in the experimental or control groups (P greater than 0.05). Thus, quercetin and rutin tested were not shown to be carcinogenic to ACI rats.

Animals↗

Carcinogenic activity of 3-amino-1-methyl-5H-pyrido [4,3-b]indole (Trp-P-2), a pyrolysis product of tryptophan.

The carcinogenic activity of 3-amino-1-methyl-5H-pyrido[4,3-b]indole (Trp-P-2), a pyrolysis product of tryptophan, was studied in inbred strain ACI rats. Twenty rats received a diet containing 0.01% Trp-P-2 for 870 days. Nineteen rats survived for more than 400 days after the start of feeding, 1 rat developed a hemangioendothelial sarcoma of the liver, and 6 rats developed neoplastic liver nodules. These liver tumors were found only in female rats that died 666--870 days after the start of feeding. No liver tumors were found in control animals.

Animals↗

Teleocidin, lyngbyatoxin A and their hydrogenated derivatives, possible tumor promoters, induce terminal differentiation in HL-60 cells.

Teleocidin isolated from Streptomyces mediocidicus, its catalytically hydrogenated compound dihydroteleocidin B, and lyngbyatoxin A isolated from marine blue-green alga Lyngbya majuscula as well as its hydrogenated product, tetrahydrolyngbyatoxin A were tested for their ability to induce differentiation of human promyelocytic leukemia cells (HL-60 cells) in culture. All of these indole alkaloids induced differentiation of HL-60 cells, characterized by increased phagocytosis, increased release of lysozyme, and morphological changes resembling macrophages. The concentrations required for the induction were 1-5 ng/ml, showing similarity to those of 12-O-tetradecanoylphorbol-13-acetate (TPA). Teleocidin, lyngbyatoxin A, and tetrahydrolyngbyatoxin A are suggested to be tumor promoters, like TPA and dihydroteleocidin B. The HL-60 cell system might be useful for screening for environmental tumor promoters.

Alkaloids↗

Immunofluorescent staining of poly(ADP-ribose) in situ in HeLa cell chromosomes in the M phase.

Randomly and synchronously growing HeLa cells were tested for poly(ADP-ribose) by direct and indirect immunofluorescent antibody techniques. Fluorescence of poly(ADP-ribose) was seen only in the nuclei of intact cells when the direct immunofluorescent antibody technique was used but in both the nuclei and cytoplasm when the indirect immunofluorescent antibody technique was used; fluorescence in the cytoplasm was nonspecific. When randomly or synchronously growing HeLa cells were fixed in acetone and treated with DNase I before incubation with fluorescein-labeled antibody, intense fluorescence was observed only in the nuclei when the direct immunofluorescent staining technique was used. Addition of 3-aminobenzamide, a potent inhibitor of poly(ADP-ribose) polymerase, with the DNase I completely abolished the fluorescence in the nuclei of synchronously and randomly growing HeLa cells, except in M-phase nuclei. These results suggest that poly(ADP-ribose) can be synthesized even in the nuclei of acetone-fixed HeLa cells from "endogenous NAD+" during incubation with fluorescent antibody and also that the fluorescence of chromosomes of HeLa cells in the M phase is, in fact, due to the in situ presence of poly(ADP-ribose), not to poly(ADP-ribose) synthesized during incubation with antibody.

Chromosomes, Human↗

Indole alkaloids: dihydroteleocidin B, teleocidin, and lyngbyatoxin A as members of a new class of tumor promoters.

Dihydroteleocidin B, which is a derivative of teleocidin from Streptomyces, showed potent tumor-promoting activity in vivo when painted on mouse skin. Although the chemical structure of dihydroteleocidin B is entirely different from those of phorbol esters, the tumor-promoting activity of dihydroteleocidin B was found to be comparable to that of 12-O-tetradecanoylphorbol 13-acetate (TPA) in vivo. Teleocidin from Streptomyces and lyngbyatoxin A and debromoaplysiatoxin from the marine blue-green alga Lyngbya majuscula induced ornithine decarboxylase activity when painted on mouse skin, their effects being similar to those of dihyroteleocidin B and TPA. 13-cis-Retinoic acid inhibited this ornithine decarboxylase induction when painted on the skin 1 hr before these natural products. These three compounds produced adhesion of human promyelocytic leukemia cells (HL-60) to the flasks and inhibited differentiation of Friend erythroleukemia cells induced by dimethyl sulfoxide. The in vitro biological potencies of teleocidin and lyngbyatoxin A were almost as great as those of dihydroteleocidin B and TPA, but that of debromoaplysiatoxin was much weaker.

9,10-Dimethyl-1,2-benzanthracene↗

Effect of methyl substitution on mutagenicity of 2-amino-3-methylimidazo[4,5-f]quinoline, isolated from broiled sardine.

2-Amino-3-methylimidazo[4,5-f]quinoline [I] is a potent mutagen isolated from broiled sun-dried sardine. [I] and its seven of derivatives, (two isomers, one demethylated derivative and four methyl-substituted derivatives), were tested for mutagenicity on Salmonella typhimurium TA98 and TA100 in the presence of S9 mix. 2-Amino-1,4-dimethylimidazo[4,5-f]quinoline was the strongest mutagen of these 8 compounds on TA98, giving 159,000 revertants/nmol (750,000 revertants/micrograms). The demethylated derivative, 2-aminoimidazo[4,5-f]-quinoline, had very weak mutagenicity, inducing only 55 revertants/nmol (200 revertants/micrograms). Compounds having a methyl group at position N-1 or N-3 of 2-aminoimidazo[4,5]f]quinoline were strong mutagens. The 1,5-dimethy-derivative was more mutagenic than 3,5-dimethyl-derivative. Introduction of a methyl group at position 4 and position 5 enhanced and reduced the mutagenicity, respectively. All the compounds tested were more mutagenic to TA98 than to TA100, but their relative orders of mutgenicity with TA98 and TA100 were the same.

Animals↗

An epidemic of swine influenza in Japan.

In a serological survey of pigs in Japan haemagglutination inhibition (HI) antibody to swine influenza virus (Hsw1N1) was first detected in 721 of 3313 (21.1 per cent) sera in 1977 and 1578 of 4946 (32.1 per cent) in 1978. The virus was prevalent in all districts of Japan but to a different extent. In contrast to the high incidence of antibody, there were few cases of infection with clinical signs and only 13 outbreaks of swine influenza were recognised in Japan from 1978 to 1979. Thirty-seven influenza viruses were isolated from nasal swabs of diseased pigs in 13 outbreaks. The subtype of most isolates was Hsw1N1 but two strains were Hsw1N2.

Animals↗

Evidence for the involvement of N-hydroxylation of 3-amino-1-methyl-5H-pyrido[4,3-b]indole by cytochrome P-450 in the covalent binding to DNA.

The involvement of N-hydroxylation of 3-amino-1-methyl-5H-pyrido[4,3-b]indole (Trp-P-2) by cytochrome P-450 in the formation of covalent binding of Trp-P-2 to DNA, the induction of his+ revertant in the Ames test, and the formation of the active metabolite were confirmed. Among four cytochrome P-450 preparations, PCB-P-448 and MC-P-448 purified from liver microsomes of polychlorinated biphenyl (PCB)- and 3-methylcholanthrene-treated rats, respectively, showed higher activities for induction of mutation by Trp-P-2 than did the other two preparations, PCB-P-450 and PB-P-450 purified from PCB-and phenobarbital (PB)-treated rats, respectively. PCB-P-448 was more active than was PB-P-450 in metabolizing Trp-P-2 to N-hydroxylated Trp-P-2 (N-hydroxy-Trp-P-2). Cytochrome P-450 with higher capacity to form the N-hydroxylated metabolite induced a larger number of his+ revertants. Larger amounts of [1-14C]Trp-P-2 bound covalently to DNA were also seen when PCB-P-448 was incubated with calf thymus DNA and reduced nicotinamide adenine dinucleotide phosphate than with PCB-P-450 and PB-P-450. The direct binding of N-[ring-3H]hydroxy-Trp-P-2 isolated by high-performance liquid chromatography to calf thymus DNA was also demonstrated. These results indicate that N-hydroxylation of Trp-P-2 is an obligatory step for the covalent binding to DNA and mutagenesis of Trp-P-2. Based on these results, we propose that N-hydroxy-Trp-P-2 produced by cytochrome P-450 is important in the exertion of the mutagenicity of Trp-P-2 as it binds to DNA.

Animals↗

Comparative studies on antibodies to poly(ADP-ribose) in rabbits and patients with systemic lupus erythematosus.

Immunochemical studies were made on the antibodies induced in rabbits against poly(ADP-ribose) and naturally-occurring antibodies in patients with systemic lupus erythematosus. Antibodies against poly(ADP-ribose) could also be induced in rabbits by oligo(ADP-ribose) associated with rat liver histones and by a complex of poly(ADP-ribose) with methylated bovine serum albumin (MBSA). The two types of antibody were inhibited to the same extent by poly(ADP-ribose). However, the antibody induced by oligo(ADP-ribose) associated with histones was inhibited by oligo(ADP-ribose) with an average chain length if 4 ADP-ribosyl units and by phosphoribosyl adenosine monophosphate (PR-AMP) but not by mono ADP-ribose, whereas that induced by poly(ADP-ribose) was practically not inhibited by these related compounds even in excess amounts. The sera of ten cases of systemic lupus erythematosus showing high antibody activity against poly(ADP-ribose) were also examined immunochemically. It was found that the antibodies of three patients showed a similar inhibitory pattern to that of antibody induced in rabbits by oligo(ADP-ribose) associated with histones, those of three patients showed a similar pattern to that of antibody produced in rabbits by poly(ADP-ribose), and the remainder did not show either pattern. These findings suggest that oligo(ADP-ribose) associated with histones may serve as antigen to elicit naturally-occuring antibodies to poly(ADP-ribose) in patients with systemic lupus erythematosus.

Animals↗

Maintenance by saccharin of membrane alterations of rat bladder cells induced by subcarcinogenic treatment with bladder carcinogens.

Saccharin is known to have a tumor-promoting effect on bladder cancer in rats, but its mechanism of action is unknown. We demonstrated that the increased agglutinability of isolated epithelial cells of the bladder in the presence of concanavalin A caused by a subcarcinogenic dose of bladder carcinogens disappeared shortly after the end of their administration. However, saccharin maintained the increased agglutinability when given continuously after administration of carcinogen. Moreover, the agglutinability of bladder cells previously exposed to a subcarcinogenic dose of bladder carcinogens increased again when saccharin was given after the agglutinability had disappeared completely.

Animals↗

Carcinogenic, Mutagenic, and Comutagenic Aromatic Amines in Human Foods.

Three recent topics related to possible exposure of humans to mutagenic and carcinogenic aromatic amines and related compounds in foods are reviewed. A food additive, AF-2,2-(2-furyl)-3-(5-nitro-2-furyl) acrylamide, was first demonstrated to be mutagenic in Escherichia coli WP-2 and then proved to be carcinogenic in experimental animals. This is an example of prediction of the carcinogenicity of a compound from results of short-term microbial tests. Pyrolysates of amino acids, proteins, and foods high in a protein contain many heterocyclic aromatic amine compounds. For example, a tryptophan pyrolysate contains two derivatives ofamino-gamma-carboline(pyridoindole), and a glutamicd acid pyrolysate contains two derivatives of djipyridoimidazole. These compounds are strong frameshift mutagens in Salmonella typhimurium. Some of them were carcinogenic in an in vitro transformation test and were also carcinogenic when injected sc into hamsters and rats and when given orally to mice. Carcinogenic aromatic amines, such as aniline, and o-toluidine and yellow OB were demonstrated to be mutagenic in the presence of the beta-carboline, norharman, with S-9 mix. Diphenylnitrosamine was also mutagenic in the presence of norharman, which is present in tobacco tar and broiled food. These mutagenicities of aniline, o-toluidine, yellow OB, and diphenylnitrosamine are discussed in relation to an evaluation of compounds as environmental carcinogens from the results of short-term microbial tests.

Animals↗