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T Tahira

Publications and source records attributed to T Tahira.

At least 55 records · Page 3Linked to original sources
PubMed1988

The inhibitory effect of thioproline on carcinogenesis induced by N-benzylmethylamine and nitrite.

Thioproline, which is readily nitrosated to form nitrosothioproline, is expected to act as a nitrite scavenger. The effect of thioproline as an inhibitor of the carcinogenesis induced by N-nitroso-N-benzylmethylamine precursors was examined. Two groups of male F-344 rats were given diet containing 0.25% N-benzylmethylamine (group I) or 0.25% N-benzylmethylamine plus thioproline (0.25% until wk 17 and then 0.5%; group II). Both groups were given drinking-water containing sodium nitrite (0.1% until wk 17 and then 0.2%). The experiment was continued for 717 days. Squamous cell carcinoma of the forestomach developed in six out of seven rats in group I and in significantly fewer, two out of nine rats, in group II. The degree of invasion by the tumours was also less in group II rats, given thioproline, than in group I. Thus thioproline suppressed carcinogenesis induced by N-benzylmethylamine and nitrite, possibly by inhibiting the in vivo nitrosation of N-benzylmethylamine.

Animals↗
PubMed1988

Molecular cloning and characterization of human ret-II oncogene.

A transformant having ret-II was obtained by transfection of NIH3T3 cells with DNA from a human sigmoid colon cancer. Comparison of the restriction map of ret-II with that of proto-ret revealed that the ret-II has rearrangements both 5' and 3' to the sequence coding for the kinase domain. However, only the upstream rearrangement was consistently observed in all transformants, suggesting that the upstream rearrangement resulted in the activation of proto-ret. The recombination point and replaced sequence of ret-II were different from those previously reported for ret (Takahashi et al., 1985). In addition, ret-II does not retain region coding for transmembrane of proto-ret. This rearrangement, however, was not detected in the original tumor DNA by Southern blot analysis.

Animals↗
PubMed1987

Activation of human c-raf-1 by replacing the N-terminal region with different sequences.

Two transformants of NIH 3T3 cells, obtained by the transfection of human colon cancer and normal colon DNAs, contained activated c-raf-1. In both the activated c-raf-1, the 5' half of the c-raf-1 sequence was replaced by sequences other than c-raf-1 as a result of recombinations which occurred at the intron between exons 7 and 8. It was suggested, however, that these recombinations, which conferred the transforming activity on the c-raf-1, occurred during the transfection. In one case analyzed, characteristic sequences were found near the breakpoint and these may be involved in the recombination. It was found, upon analysing the structure of the cDNA derived from one of the activated c-raf-1, that fused mRNA had been transcribed from the recombined gene comprising the non-raf gene and c-raf-1. The mRNA possibly encodes a fused protein. One cDNA clone was derived from alternatively spliced mRNA, although its physiological role is unclear. On comparing the structure of the two human activated c-raf-1 and the rat activated c-raf which we have reported previously, it was revealed that, in these three cases, the sequences joined to the truncated c-raf(-1)1 were different. It was suggested from data which we and others have previously reported that various sequences could be capable of activating c-raf(-1) by replacing its 5' half.

Amino Acid Sequence↗
PubMed1987

Recently identified nitrite-reactive compounds in food: occurrence and biological properties of the nitrosated products.

Various Japanese foodstuffs are directly-acting mutagens in Salmonella typhimurium TA100 after nitrite treatment. Such mutagen precursors include tyramine and beta-carboline derivatives, isolated from soya sauce, and indole-3-acetonitrile, 4-methoxyindole-3-acetonitrile and 4-methoxyindole-3-aldehyde, isolated from fresh Chinese cabbage. A mutagen produced from tyramine with nitrite was found to be 4-(2-aminoethyl)-6-diazo-2,4-cyclohexadienone (3-diazotyramine), and one produced from indole-3-acetonitrile with nitrite to be 1-nitrosoindole-3-acetonitrile. These two mutagens were directly-acting mutagens not only in S. typhimurium TA100 and TA98 but also in Chinese hamster lung cells, using diphtheria toxin resistance as a selective marker. The carcinogenicity of 3-diazotyramine was demonstrated in male Fischer 344 rats. Tyramine, beta-carboline and indole compounds are present ubiquitously in our environment, especially in foods. Therefore, the role of these newly identified mutagen precursors in the development of human cancer should be taken into consideration.

Acetonitriles↗
PubMed1986

Thapsigargin, a histamine secretagogue, is a non-12-O-tetradecanoylphorbol-13-acetate (TPA) type tumor promoter in two-stage mouse skin carcinogenesis.

Thapsigargin, a hexaoxygenated tetraacylated sesquiterpene lactone, induced irritation of mouse ear and histidine decarboxylase (HDC) activity in mouse skin, but it did not induce ornithine decarboxylase in mouse skin or adhesion of human promyelocytic leukemia (HL-60) cells. Although thapsigargin did not give consistent positive results in a short-term screening system for tumor promoters, it was tested in a two-stage carcinogenesis experiment on mouse skin. The potency of thapsigargin to induce HDC in mouse skin was used to determine the dose in this experiment. Application of 10 micrograms (17 nmol) thapsigargin induced HDC activity of 139 pmol CO2/mg protein per 60 min. Tumors were found in the skin of 53.5% of the mice treated with DMBA plus 5 micrograms (8.5 nmol) thapsigargin in week 22, in none of those treated with thapsigargin alone by week 30. One tumor appeared in 1 of 15 mice treated with DMBA alone in week 21. Thapsigargin cannot bind to the phorbol ester receptor in the particulate fraction of mouse skin and so is classified as a non-12-O-tetradecanoylphorbol-13-acetate (TPA) type tumor promoter. It is a new tumor promoter differing in many respects from the well-defined TPA type tumor promoters. Several naturally occurring analogues of thapsigargin, such as thapsigargicin and thapsitranstagin, might also be new non-TPA type tumor promoters, because thapsigargicin and thapsitranstagin induced irritation of mouse ear and HDC activity in mouse skin.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1986

Mutagenicity of soy sauce treated with a physiologically feasible concentration of nitrite.

Soy sauce treated with nitrite was found to be more mutagenic to Escherichia coli WP2 uvrA/pKM101 than Salmonella typhimurium TA100 without S9 mix. The mutagenicity of soy sauce treated with nitrite was affected by the concentration of soy sauce in the nitrosation mixture, and a concentration of 5% resulted in the highest specific activity (revertants/ml soy sauce equivalent). By incubating soy sauce at a concentration of 5% in a solution of 1 mM nitrite at pH 3 for 1 h at 37 degrees C, the equivalent of 1 ml of soy sauce induced 2790 revertants of E. coli WP2 uvrA/pKM101 without S9 mix.

Biotransformation↗
PubMed1986

4-Methoxyindole derivatives as nitrosable precursors of mutagens in Chinese cabbage.

Two indole compounds isolated from fresh Chinese cabbage were shown to be mutagen precursors that yielded direct-acting mutagens on treatment with nitrite. They were identified as 4-methoxyindole-3-acetonitrile and 4-methoxy-indole-3-aldehyde. When these compounds were treated with 50 mM nitrite at pH 3.0 for 1 h at 37 degrees C, 4-methoxyindole-3-acetonitrile induced 31,800 and 10,000 revertants of Salmonella typhimurium TA100 and TA98, respectively, per mg of mutagen precursor in the absence of S9 mix, and 4-methoxyindole-3-aldehyde induced 156,900 revertants of TA100 and 26,800 revertants of TA98 per mg in the absence of S9 mix.

Acetonitriles↗
PubMed1986

Structure of the c-Ki-ras gene in a rat fibrosarcoma induced by 1,8-dinitropyrene.

Restriction enzyme maps were made of the region around exons 1 and 2 of activated c-Ki-ras of a fibrosarcoma (1,8-DNP2) induced in a rat by 1,8-dinitropyrene. Nucleotide sequence analysis revealed that activated c-Ki-ras shows a G----T transversion in codon 12 and consequently encodes cysteine instead of glycine in normal rat c-Ki-ras.

Amino Acid Sequence↗
PubMed1986

Nucleotide sequence of exon I of the rat c-K-ras gene.

We have isolated a DNA fragment containing exon I of rat cellular proto-oncogene of K-ras and sequenced the exon I. The obtained sequence was compared with that of the corresponding region in viral oncogene of Kirsten strain of murine sarcoma virus (Ki-MSV). The results showed that the exon I sequences of cellular K-ras genes in rat and human cells could encode the same amino acid sequence, while the viral K-ras gene could code for two different amino acids corresponding to the 12th and 37th positions from the N-terminus of K-ras gene product. The amino acid substitutions found between viral and cellular K-ras genes are discussed in relation to the transforming ability of Ki-MSV.

Animals↗
PubMed1986

Activation of rat and human c-raf(-1) by rearrangement.

Activated c-raf(-1) gene was found in three transformants obtained by transfecting DNAs from rat hepatocellular carcinoma, metastasis of human colon cancer in mesocolon and normal mucosa from a different colon cancer patient. Rat and human activated c-raf(-1) genes were cloned into cosmid vectors; restriction enzyme mapping revealed both activated c-raf(-1) genes to have rearrangement in the center of the normal form of the gene, and the upstream sequences were replaced by unrelated sequences. Using genomic DNA fragments located immediately downstream of the recombination points, the activations of all these c-raf(-1) were shown to have occurred during the transfection process. The recombination points in both the rat and human clones isolated were located in the intron between exons 7 and 8, and nucleotide sequencing around these recombination points showed there to be an inverted repeat which could be involved in inducing in vitro recombination. Nucleotide sequencing of rat and human c-raf(-1) cDNAs revealed the upstream sequences, recombined to the 3' half of c-raf(-1), to be expressed as fusion mRNAs; the production of fused proteins was predicted from a long open reading frame, which is in-frame with the kinase domain encoded from the 3' half of the c-raf(-1) gene. There is a cysteine clustering region in an N-terminal region of the c-raf(-1) product deduced from the nucleotide sequence, and this cysteine clustering region was found to be highly homologous to that present in an N-terminal region of protein kinase C, although, in the latter cysteine clusters are present in duplicate. From analogy with the activation mechanism of protein kinase C, the N-terminal region of serine/threonine kinase coded by the c-raf(-1) gene is suggested to be a regulatory part of the enzyme activity, and it proposed that the replacement or truncation of this regulatory part could be the mechanism whereby c-raf(-1) is activated.

Amino Acid Sequence↗
PubMed1985

Appearance of direct-acting mutagenicity of various foodstuffs produced in Japan and Southeast Asia on nitrite treatment.

After nitrite treatment, various kinds of pickled vegetables and sun-dried fishes produced in Japan showed direct-acting mutagenicity on Salmonella typhimurium TA100, inducing 1900-18000 revertants/g. Kimchis, sun-dried fishes, sun-dried squid, soy sauces, fish sauces, bean pastes and shrimp paste produced in Korea, the Philippines and Thailand also showed direct-acting mutagenicity after nitrite treatment. All soy sauces and fish sauces tested contained as much tyramine as 17-1020 micrograms/ml, but very low or undetectable amounts of (-)-(1S,3S)- and (-)-(1R,3S)-1-methyl-1,2,3,4-tetrahydro-beta-carboline-3-carboxylic acids.

Animals↗
PubMed1985

Activation of K-ras and oncogenes other than ras family in rat fibrosarcomas induced by 1,8-dinitropyrene.

Oncogenes of fibrosarcomas of rats, induced by subcutaneous injection of 1,8-dinitropyrene (1,8-DNP), were examined by NIH 3T3 cell transfection assay and Southern blot analysis. Transformants containing rat specific repetitive sequences were obtained with DNAs of 4 fibrosarcomas, 1,8-DNP1, 1,8-DNP2, 1,8-DNP3 and 1,8-DNP7. A transformant, 1,8-DNP2-2, induced by DNA of a fibrosarcoma, 1,8-DNP2, and 7 secondary transformants derived from it contained rat K-ras sequences. Another transformant, 1,8-DNP2-1, induced by the same sarcoma did not have a ras family oncogene. This indicates that the sarcoma, 1,8-DNP2, has at least 2 transforming genes. The transforming genes of 6 other transformants derived from 3 sarcomas did not contain ras family or neu transforming genes.

Animals↗
PubMed1985

Effect of sinomenine on antibody responses in mice.

Sinomenine, an epimorphinan alkaloid, was tested for the immunosuppressive effect in mice. This compound produced a decrease of plaque-forming cells (PFC) to a T cell-dependent antigen, sheep red blood cells, in vivo. The depression of the PFC response induced with sinomenine was dose and time dependent. On the other hand, it failed to suppress the PFC response to a T cell-independent antigen, lipopolysaccharide. The immunosuppressive dose of sinomenine did not alter the cellularity of spleen, thymus, bone marrow and peripheral blood leucocytes, the DNA synthesis activity of bone marrow cells nor the proliferative responses of spleen cells induced by T cell and B cell mitogens in unprimed mice. These data suggest a selective effect of sinomenine on lymphoid cells. This compound has a potential for use in studies of immuno-deficiencies or clarifying some aspect of immunity.

Animals↗
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↗
PubMed1984

Estimation of tumor promoting activity and structure-function relationships of aplysiatoxins.

Twelve aplysiatoxin compounds have been evaluated as possible tumor promoters in vivo by means of three biological tests: viz. irritation of mouse ear, induction of ornithine decarboxylase in dorsal skin of mice, and inhibition of specific binding of [3H]12-O-tetradecanoylphorbol-13-acetate (TPA) to an epidermal particulate fraction. The potencies of these three biological activities correlate well for each derivative. Bromoaplysiatoxin shows biological activities that are similar to those of the strong tumor promoter, aplysiatoxin. The present studies suggest that the C-3, C-20 and C-30 hydroxyl groups of the aplysiatoxins are involved in binding to the specific receptor of TPA.

Animals↗
PubMed1984

Kinetics of nitrosation of thioproline, the precursor of a major nitroso compound in human urine, and its role as a nitrite scavenger.

The kinetics of nitrosation of thioproline was studied. The rate of the reaction increased with decrease in pH, and was first-order with respect to nitrite concentration. The reaction rate was proportional to the concentration of total thioproline (free plus protonated), not to that of free thioproline. The initial reaction rate followed the equation: rate = k4 X [thioproline] X [NaNO2] X [H+] The rate constant was found to be 49.4M-2 . sec-1 at pH 2.0 and 37 degrees. Thioproline acted as a nitrite scavenger, and suppressed the formation of a carcinogen, N-nitroso-N-benzylmethylamine, from N-benzylmethylamine and nitrite. More than 90% of the formation of N-nitroso-N-benzylmethylamine was inhibited by adding 20mM thioproline to a reaction mixture containing 20mM N-benzylmethylamine and 20mM sodium nitrite at pH 3.0 and 37 degrees.

Antineoplastic Agents↗