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Biomedical subjects

T Sugimura

Publications and source records attributed to T Sugimura.

At least 649 records · Page 36Linked to original sources
PubMed1985

Absence of carcinogenicity of 1-nitropyrene, correction of previous results, and new demonstration of carcinogenicity of 1,6-dinitropyrene in rats.

1-Nitropyrene (1-NP), 1,6-dinitropyrene (1,6-DNP) and 1,8-dinitropyrene (1,8-DNP), which are potent mutagenic components of diesel exhaust and air pollutants, were injected subcutaneously into the back of F344 rats. No tumor was induced by experimental day 650 in rats treated with 40 or 4 mg of 1-NP. On the other hand, 1,6-DNP at a total dose of 4 mg was demonstrated to induce sarcomas at the injection site in all 10 rats. 1,8-DNP at total doses of 0.4 and 0.04 mg also induced sarcomas in 10 and 9 out of 10 rats, respectively, by day 320. Our previous finding that 1-NP was carcinogenic was possibly due to contamination of the preparation with dinitropyrenes.

Animals↗
PubMed1985

Complete nucleotide sequence of an infectious clone of human T-cell leukemia virus type II: an open reading frame for the protease gene.

The entire nucleotide sequence of an infectious clone of human T-cell leukemia virus type II provirus was determined. This provirus consists of 8952 nucleotides. In addition to long terminal repeats and gag, pol, env, and X, a protease gene that is responsible for processing the gag precursor protein was found. The protease gene is encoded in a different frame from gag and pol and was located between the gag and pol open reading frames. The 5' region of the protease gene overlaps the 3' gag region. Coding regions of the provirus show about 60% homology with those of human T-cell leukemia virus type I at the nucleotide level. The evolutionary relationship between human T-cell leukemia virus types I and II is discussed.

Antigens, Viral↗
PubMed1985

Molecular cloning of an activated human oncogene, homologous to v-raf, from primary stomach cancer.

Transfection with high molecular weight DNA from a primary stomach cancer induced foci of transformed NIH 3T3 cells, and the transformed cells were tumorigenic in nude mice. By screening with a human Alu-family probe, we isolated the human DNA sequence from the secondary transformant cells. This transforming sequence encompasses about 60 kilobase pairs and is unrelated to known human transforming genes. Examination of homologies between this sequence and retroviral oncogenes revealed that the human transforming sequence is closely related to the v-raf oncogene of murine transforming retrovirus 3611-MSV.

Animals↗
PubMed1985

Identification of new gene products coded from X regions of human T-cell leukemia viruses.

Antibodies were raised against oligopeptides deduced from the nucleotide sequence in the conserved region located between env and the 3' long terminal repeat in human T-cell leukemia virus type I (HTLV-I) and type II (HTLV-II) to detect a protein coded from this region in virus-infected cells. Two of these antibodies precipitated a protein of 41 kilo-daltons in HTLV-I-infected cell lines and a protein of 38 kilo-daltons in HTLV-II-infected cells. The protein in HTLV-I-infected cells was precipitated by plasma from patients with adult T-cell leukemia but not by plasma from a normal adult. These results indicate that these proteins were translated from new coding regions (X) present in HTLV-I and HTLV-II.

Base Sequence↗
PubMed1985

Quantification of 2-amino-3-methylimidazo[4,5-f]quinoline (IQ) and 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) in beef extracts by liquid chromatography with electrochemical detection (LCEC).

A simple and sensitive method was developed for quantification of mutagenic/carcinogenic aminoimidazoquinoline and aminoimidazoquinoxaline compounds in heated materials. Samples were partially purified by blue-cotton treatment, 0.1 N HCl-methylene dichloride partition and separation in a SEP-PAK silica cartridge. The recoveries of aminoimidazoquinoline and aminoimidazoquinoxaline compounds at the step of partial purification were estimated by spiking with 14C-labeled compounds. The compounds in partially purified materials were analyzed by liquid chromatography with electrochemical detection using a combination of two columns of octadecyl silane and cation exchange. Bacteriological-grade beef extract was found to contain 41.6 and 58.7 ng/g of 2-amino-3-methylimidazo[4,5-f]quinoline and 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx), respectively. MeIQx was also detected at a level of 3.1 ng per g in food-grade beef extract.

Animals↗
PubMed1985

Flavone modulators of rat hepatic aryl hydrocarbon hydroxylase.

The cytochrome P-450-dependent aryl hydrocarbon hydroxylase (AHH) metabolizes a wide variety of endogenous and exogenous compounds to nontoxic metabolites and/or toxic products. We have utilized a series of 18 flavone modulators of AHH to distinguish and probe for different cytochrome P-450 isozymes in liver microsomes from control and 3-methylcholanthrene (MC)-injected rats. some flavones (maackiain acetate, flavanone, mollisacacidin, embinin, sciadopitysin) activated, while most of the tested compounds inhibited the MC-induced type of AHH. Although all flavones either inhibited or had little effect on the constitutive AHH in microsomes from control rats, the degree of inhibition varied greatly: some flavones (chrysin, chrysoeriol, baicalein, maackiain acetate, isoliquiritigenin, sciadopitysin) inhibited over 75% of the AHH. The various flavones we screened may prove useful in defining the cytochrome P-450 content of tissues and for probing the active sites of individual isozymes. The modulatory effects of the naturally occurring flavones assume additional importance in that they may be factors in animal and human responsiveness to cytochrome P-450 substrates.

Animals↗
PubMed1985

Inhibition of teleocidin-caused epidermal ornithine decarboxylase induction by phospholipase A2-, cyclooxygenase- and lipoxygenase-inhibitors.

Teleocidin (5 micrograms/mouse), a potent tumor promoting indole alkaloid from Streptomyces, induced epidermal ornithine decarboxylase (ODC) in CD-1 mice. Teleocidin-caused ODC induction was inhibited by the treatment of indomethacin (2 mumol/mouse), a selective cyclooxygenase inhibitor, and p-bromophenacyl bromide (BPB) (30 mumol/mouse), a phospholipase A2 inhibitor. Teleocidin-caused ODC induction inhibited by indomethacin was completely restored by concurrent application of prostaglandin E2 (PGE2) (140 nmol/mouse). On the other hand, teleocidin-caused ODC induction inhibited by BPB was not restored by the treatment of mice with PGE2, but partially restored by the treatment with arachidonic acid (1 mumol/mouse). Treatment of mice with lipoxygenase inhibitors such as BW755C (30 mumol/mouse), nordihydroguaiaretic acid (NDGA) (30 mumol/mouse), quercetin (10 mumol/mouse), and 2,3,5-trimethyl-6-(12-hydroxy-5,10-dodecadiynyl)-1,4-benzoquinone (AA861) (10 mumol/mouse) clearly suppressed ODC induction by teleocidin. Moreover, both NDGA (30 mumol/mouse) and quercetin (10 mumol/mouse) inhibited the restoring effect of PGE2. Therefore, our present results suggest that arachidonate metabolites, i.e., not only cyclooxygenase product(s) but also lipoxygenase product(s), are involved in the mechanism of ODC induction by teleocidin.

Animals↗
PubMed1985

Structure of the pX protein deduced from the nucleotide sequence of a cDNA clone of pX mRNA in cells infected with human T-cell leukemia virus type I.

A splice donor site of pX mRNA of human T-cell leukemia virus type I was elucidated by analyzing a cDNA clone of poly A+ RNA isolated from cat fibroblast cells infected with the virus. The donor site was located near the 5' end of the env gene. The putative N-terminal amino acid sequence of the pX protein was deduced to be Met-Ala-His---.

Amino Acid Sequence↗
PubMed1985

Myristylation of gag protein in human T-cell leukemia virus type-I and type-II.

We found that p19gag of HTLV-I and p23gag of HTLV-II are myristylated. The p28, which is immunologically cross-reactive with monoclonal antibody against p19gag of HTLV-I was also shown to be myristylated in the HTLV-I-infected cell lines MT-2 and HUT102. However, no myristylated p28 was found in HTLV-II-infected cell lines, Mo and Ton1.

Antibodies, Monoclonal↗
PubMed1985

Carcinogenicities in mice and rats of IQ, MeIQ, and MeIQx.

The mutagenic heterocyclic amines, 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) are present in broiled fish, fried beef, and beef extract. Their carcinogenicities in CDF1 mice and F344 rats were tested by their oral administration in the diet. In mice given diet containing 0.03% IQ, tumors developed in the liver (hepatocellular carcinomas or hepatocellular adenomas), forestomach (squamous cell carcinomas or papillomas), and lung (adenocarcinomas or adenomas) at high incidences. In mice given diet containing 0.04% or 0.01% MeIQ, squamous cell carcinomas and papillomas of the forestomach developed at high incidences. About 40% of the squamous cell carcinomas induced in the forestomach by 0.04% MeIQ metastasized to the liver. Clear dose-response relations were seen in the incidences of tumors in the groups given 0.04% and 0.01% MeIQ. The squamous cell carcinoma-papilloma ratios were higher in 0.04% groups than in 0.01% groups. Female mice treated with 0.04% and 0.01% MeIQ showed significantly higher incidences of liver tumors than controls. The experiment on the carcinogenicity of MeIQx at a dose of 0.06% in mice is still in progress but by experimental week 74, 4 of 16 males and 7 of 18 females autopsied were found to have liver tumors. Rats given diet containing 0.03% IQ showed high incidences of hepatocellular carcinomas, adenocarcinomas of the small and large intestines, and squamous cell carcinomas of the Zymbal gand, clitoral gland, and skin. Except for the liver, the target organs of IQ in CDF1 mice and F344 rats were different.

Adenocarcinoma↗
PubMed1985

Nitrosatable precursors of mutagens in vegetables and soy sauce.

Nitrosatable precursors of mutagens that show mutagenicity to Salmonella typhimurium TA100 without S9 mix after treatment with nitrite at pH 3 were found in various foods. From Chinese cabbage, three indole compounds, indole-3-acetonitrile, 4-methoxyindole-3-acetonitrile, and 4-methoxyindole-3-aldehyde, were identified as mutagen precursors. 1-Methylindole and 2-methylindole, which are present in cigarette smoke showed strong mutagen precursor activity. Escherichia coli WP2 uvrA/pKM101 is more sensitive than S. typhimurium TA100 to nitrosatable precursors in soy sauce after treatment with 1-3 mM nitrite. The mutagenicity of soy sauce towards E. coli WP2 uvrA/pKM101 is partly explained by 1-methyl-1,2,3,4-tetrahydro-beta-carboline-3-carboxylic acid (MTCA) and tyramine reported previously. Oral administration of soy sauce and nitrite to male Fischer 344 rats for 2 years induced basal cell proliferation of the forestomach and intestinal metaplasia of the glandular stomach, but did not induce cancers in any organ. 3-Diazotyramine, a mutagenic nitrosation product of tyramine that is present at high concentrations in various foods induced squamous cell carcinomas of the oral cavity of rats when given in their drinking water. The carcinogenesis by N-benzylmethylamine, a nitrosatable precursor and nitrite was prevented by thioproline.

Animals↗
PubMed1985

A blue-green alga from Okinawa contains aplysiatoxins, the third class of tumor promoters.

The causative agents of swimmer's itch were isolated from the marine blue-green alga, Lyngbya majuscula, which grows off the coast of the Okinawa islands, Japan. Nuclear magnetic resonance and mass spectral studies revealed that these agents were identical with aplysiatoxin and debromoaplysiatoxin, which were previously shown to be the causative agents of swimmer's itch in Hawaii. Aplysiatoxin and debromoaplysiatoxin were recently found to be potent tumor promoters in two-stage carcinogenesis in mouse skin. This is the first report that humans are directly affected by these potent environmental tumor promoters in Japan.

Animals↗
PubMed1985

Activation of c-Ki-ras gene in human pancreatic cancer.

DNA isolated from a lymph node with metastasis from pancreatic adenocarcinoma in a Japanese male patient transformed NIH3T3 cells upon transfection by the calcium-phosphate precipitation technique. Analysis of DNA from the transformant revealed the presence of an activated human c-Ki-ras gene, which is considered to be responsible for the transformation of the NIH3T3 cells.

Adenocarcinoma↗
PubMed1985

Correlation of results of agglutination assays with concanavalin A and carcinogenesis experiments on promoters of bladder cancer.

The promoting effects of various chemicals and dietary constituents on bladder carcinogenesis were examined by means of a short-term assay, in which maintenance of concanavalin A agglutination of isolated rat bladder cells caused by a subcarcinogenic dose of N-butyl-N-(4-hydroxybutyl)nitrosamine was used as an indicator. Twenty-seven chemicals were examined as possible promoters. Positive results in this assay were consistent with established promoting effects in the cases of sodium saccharin, saccharin, sodium L-ascorbate, sodium cyclamate, DL-tryptophan, butylated hydroxyanisole, butylated hydroxytoluene, L-thioproline and phenacetin. Allopurinol was the only established promoter that gave negative results in the agglutination assay. Thus, this method is useful for rapid evaluation of the specific promoting effect of a chemical on bladder carcinogenesis.

Agglutination Tests↗
PubMed1984

Reduction by N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide (W-7), a calmodulin antagonist, in the number of phorbol ester receptors in mouse skin.

A calmodulin antagonist, N-(6-aminohexyl)-5-chloro-1-naphthalene-sulfonamide (W-7), reduced the number of phorbol ester receptors in mouse skin in a dose- and time-dependent manner. The reduction occurred immediately after topical application of 30 mumoles of W-7, reaching a maximum of 86% after 5 min. Reduction in specific binding of 12-O-tetra-decanoylphorbol-13-acetate can explain the antitumor promoting activity of W-7 in mouse skin.

Animals↗