Biomedical subjects

T Sugimura

Publications and source records attributed to T Sugimura.

At least 595 records · Page 33Linked to original sources

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

Mutagenicity of quercetin in Chinese hamster lung cells in culture.

Quercetin, a flavonol that is widely distributed in edible plants, was assayed for cytotoxic and mutagenic activities on Chinese hamster lung cells in culture, using diphtheria toxin resistance as a selective marker. Results showed that it was cytotoxic, and induced a dose-dependent increase in the number of diphtheria-toxin-resistant mutants in the absence of a metabolic activation system.

Animals↗

PubMed1986

N-acetyl derivative as the major active metabolite of 2-amino-6-methyldipyrido[1,2-a:3',2'-d]imidazole in rat bile.

2-Amino-6-methyldipyrido[1,2-a:3',2'-d]imidazole (Glu-P-1) is a mutagen and carcinogen isolated from a glutamic acid pyrolysate. When this 14C-labeled compound was administered to male F344 rats at a dose of 0.3 mCi (20.8 mg)/kg b.w., 70% of the radioactivity was excreted into the bile in 24 h. On HPLC analysis of this bile, several metabolites of Glu-P-1 were found with unmetabolized Glu-P-1. One of the mutagenic metabolites was identified as N-acetyl-Glu-P-1. This metabolite had a specific mutagenic activity of about one quarter of that of Glu-P-1 and its amount in the bile corresponded to a few percent of the dose of Glu-P-1 administered.

Animals↗

PubMed1986

Activation of rat c-raf during transfection of hepatocellular carcinoma DNA.

Rat c-raf was found to be activated in a transformant obtained with DNA of a hepatocellular carcinoma induced by 2-amino-3-methylimidazo[4,5-f]quinoline. This activated c-raf was cloned in a cosmid vector and actively transforming clones were obtained. Comparison of the restriction maps of this activated c-raf and cloned normal rat c-raf revealed a recombination in the 5'-terminal region of the activated form of this gene. The recombined DNA was shown to be actively transcribed and possibly to form a fused mRNA with c-raf, which is slightly smaller than normal c-raf mRNA. Since this recombination was not detected in the original tumor by Southern blot analysis, it presumably occurred during transfection.

Animals↗

PubMed1986

Transforming gene from human stomach cancers and a noncancerous portion of stomach mucosa.

DNAs from 21 human stomach cancers, 16 metastatic stomach cancers to lymph nodes, and 21 apparently noncancerous specimens of stomach mucosae from a total of 26 patients with stomach cancer were tested for their ability to induce neoplastic transformation of NIH 3T3 cells on transfection by the calcium phosphate precipitation technique. Three samples of DNA were shown to have transforming activity; one was from a primary stomach cancer of one patient, the second was from a noncancerous portion of stomach mucosa of the same patient, and the third was from a lymph node metastasis of stomach cancer from another patient. These transformants were tumorigenic in nude mice, and DNAs from the cells could induce secondary transformants. A portion of the transforming gene from the stomach cancer of one patient, which contained the sequences expressed in the NIH 3T3 transformants, was cloned. The transforming gene did not have any homology with the transforming sequences reported previously. We have applied the term hst to this novel human transforming gene. The transforming gene, hst, was found to be present in all the primary and secondary transformants induced by the other two samples of DNA.

Adenocarcinoma↗

PubMed1986

Adult T-cell leukemia/lymphoma not associated with human T-cell leukemia virus type I.

We describe five patients with adult T-cell leukemia/lymphoma (ATL) with neither integration of human T-cell leukemia virus type I (HTLV-I) into their leukemia cells nor anti-HTLV-I antibody in their sera. These findings indicate that HTLV-I may not have been involved in leukemogenesis in these patients. The clinicohematological, cytopathological, and immunological features of HTLV-I-negative ATL were exactly the same as those of HTLV-I-associated ATL. Leukemia cells with pleomorphic nuclei, generalized lymphadenopathy, hepatosplenomegaly, skin lesions, hypercalcemia, and elevated lactate dehydrogenase levels, all of which are characteristic features of typical ATL, were also seen in these patients with HTLV-I-negative ATL. Leukemia cells expressed T3, T4, and pan-T-cell antigens in three cases, and T3 and pan-T-cell antigens in two. All five patients had lived in ATL-nonendemic areas. The finding of HTLV-I-negative ATL suggests that factor(s) other than HTLV-I infection may be involved in ATL leukemogenesis.

Adult↗

PubMed1986

Transforming activity of human papillomavirus type 16 DNA sequence in a cervical cancer.

A genomic DNA sample from cervical cancer tissue, containing human papillomavirus (HPV) type 16, was found to induce malignant transformation of NIH 3T3 cells when it was tested by transfection assays using the calcium phosphate coprecipitation technique. The primary and secondary transformants contained the HPV type 16 DNA sequences and human specific Alu family sequences. To the best of our knowledge, it has not been reported previously that HPV type 16 DNA sequences in total genomic DNA from a cervical cancer have transforming activity.

Adenocarcinoma↗

PubMed1986

Induction of hepatocellular carcinoma and highly metastatic squamous cell carcinomas in the forestomach of mice by feeding 2-amino-3,4-dimethylimidazo[4,5-f]quinoline.

2-Amino-3,4-dimethylimidazo[4,5-f]quinoline (MeIQ), a potent mutagen which was isolated from grilled sardines, was tested for carcinogenicity in CDF1 mice. Mice were given diet containing 0.04 or 0.01% MeIQ for 91 weeks. The incidences of liver tumors (hepatocellular carcinomas and hepatocellular adenomas) in female mice given 0.04 and 0.01% MeIQ were significantly higher than those in controls. The incidences of forestomach tumors (squamous cell carcinomas and papillomas) were also significantly higher in both sexes of mice given MeIQ. About 40% of the squamous cell carcinomas that developed in mice given diet containing 0.04% MeIQ metastasized to the liver.

Animals↗

PubMed1986

Binding studies of [3H]lyngbyatoxin A and [3H]debromoaplysiatoxin to the phorbol ester receptor in a mouse epidermal particulate fraction.

The preparation of [3H]lyngbyatoxin A by catalytic triton-proton exchange of lyngbyatoxin A and [3H]debromoaplysiatoxin by tritiation-debromination of aplysiatoxin is described. The dose-response curves for the binding of [3H]lyngbyatoxin A and [3H]debromoaplysiatoxin to a mouse epidermal particulate fraction are virtually the same as the one previously described for [3H]12-O-tetradecanoylphorbol-13-acetate ([3H]TPA). The specific binding of [3H]TPA, [3H]-lyngbyatoxin A and [3H]debromoaplysiatoxin to the mouse epidermal particulate fraction is inhibited to the same degree by unlabeled TPA, teleocidin, lyngbyatoxin A, aplysiatoxin and debromoaplysiatoxin. This study indicates that TPA, lyngbyatoxin A and debromoaplysiatoxin bind to the same high affinity receptor in mouse skin.

Animals↗

PubMed1986

Palytoxin is a non-12-O-tetradecanoylphorbol-13-acetate type tumor promoter in two-stage mouse skin carcinogenesis.

Palytoxon, which is a toxin with a molecular weight of 2681 daltons isolated from a marine coelenterate, is a potent skin irritant. However, it did not induce ornithine decarboxylase in mouse skin, or adhesion of human promyelocytic leukemia cells (HL-60). Moreover, it did not inhibit the specific binding of [3H]12-O-tetradecanoylphorbol-13-acetate (TPA) to a mouse skin particulate fraction or activate protein kinase C isolated from mouse brain in vitro. Since palytoxin showed strong irritation on mouse ear in one short-term screening test for a promoter, it was examined in a two-stage carcinogenesis experiment. The incidence of tumors in a group of mice treated with 7,12-dimethylbenz[a]anthracene plus palytoxin was 62.5% in week 25. These tumors were identified histologically as seven papillomas and one carcinoma. This paper reports the potent tumor-promoting activity of palytoxin, which is classified as a non-TPA-type tumor promoter.

9,10-Dimethyl-1,2-benzanthracene↗

PubMed1986

Sequential histologic changes during gastric carcinogenesis induced by N-methyl-N'-nitro-N-nitrosoguanidine in susceptible ACI and resistant BUF rats.

Sequential histologic changes of the stomach during carcinogenesis induced by N-methyl-N'-nitro-N-nitrosoguanidine (MNNG; CAS: 70-25-7) were studied in susceptible ACI and resistant BUF strain rats. Rats were given MNNG at a concentration of 83 micrograms/ml in their drinking water for 32 weeks and then tap water and were sacrificed sequentially between weeks 1 and 57. In ACI rats, erosions, regenerative changes, focal and slightly atypical changes, and diffuse and severe atypical changes were observed sequentially in the pyloric region during the period of MNNG administration, where adenocarcinomas were observed after the cessation of MNNG treatment. In BUF rats, the main histologic changes induced by MNNG were erosions and hyperplasia of the glandular portion of pyloric glands at the margin of erosions. After the cessation of MNNG treatment, the hyperplasia of the pyloric glands subsided and was followed by atrophy of these glands. The results suggested that the responses of the gastric mucosa to MNNG in ACI and BUF rats were qualitatively different.

Adenocarcinoma↗

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

Metabolic aspects of pyrolysis mutagens in food.

The first step in metabolic activation of mutagenic and carcinogenic heterocyclic amines has been elucidated to be N-hydroxylation by cytochrome P-448. N-Hydroxyamino compounds are further activated to form N-O-acyl derivatives that readily react with DNA. The adducts between the metabolites of Trp-P-2 and Glu-P-1 and DNA were shown to have a C8-guanylamino structure. In the case of Glu-P-1, modification of guanine in GC clusters occurred preferentially. Glutathione transferases and myeloperoxidase were shown to inactivate some heterocyclic amines or their active metabolites. Hemin and fatty acids bind to and inactivate them. Fibers and other factors from vegetables also work to inactivate heterocyclic amines. Nitrite at low pH also degraded some heterocyclic amines, but those with an imidazole moiety were resistant. Glu-P-1 induced intestinal tumors in a high incidence when fed orally to rats. When 14C-Glu-P-1 was administered by gavage into rats about 50% and 35% were excreted into feces and urine, respectively, within 24 hr. When the bile was collected, around 60% of radioactivity was excreted into it within 24 hr. In the bile, N-acetyl-Glu-P-1 was identified as one of the metabolites of Glu-P-1. It showed a mutagenic activity of about one fourth that of Glu-P-1 with S9 mix. Some radioactivity was also detected in the blood. At 24 hr after administration, most of the radioactivity was found to be bound to erythrocyte beta-globins and serum proteins including albumin.

Animals↗

PubMed1986

Mutagenic activities of heterocyclic amines in Chinese hamster lung cells in culture.

A mutation assay system with Chinese hamster lung cells (CHL) using diphtheria toxin resistance as a selective marker has been established. The mutagenic activities of heterocyclic amines, originally isolated from pyrolyzates of amino acids and proteins, broiled fish and fried beef were assayed in cultured CHL cells in the absence and presence of a metabolic activation system, with diphtheria toxin resistance as a marker. All the heterocyclic amines tested except 3-amino-1,4-dimethyl-5H-pyrido [4,3-b]indole (Trp-P-1) required the presence of a metabolic activation system for mutagenicity on CHL cells. 3-Amino-1-methyl-5H-pyrido[4,3-b]indole (Trp-P-2) was the most mutagenic among the heterocyclic amines tested. Other compounds were also mutagenic in the following order of decreasing potency: 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).

Animals↗

PubMed1986

Carcinogenicity in mice and rats of heterocyclic amines in cooked foods.

Carcinogenicities of mutagenic heterocyclic amines in cooked foods have been tested in CDF1 mice and F344 rats of both sexes. Eight heterocyclic amines--Trp-P-1, Trp-P-2, Glu-P-1, Glu-P-2, MeA alpha C, A alpha C, IQ, and MeIQ--were given to mice and/or rats at 0.02 to 0.08% in the diet continuously. In mice, all heterocyclic amines tested were demonstrated to be carcinogenic. Hepatocellular carcinomas were induced in a high incidence in all groups treated with heterocyclic amines. Hemangioendothelial sarcomas were also induced by Glu-P-1, Glu-P-2, MeA alpha C, and A alpha C. Most hemangioendothelial sarcomas were located in the interscapular brown adipose tissue. In mice given IQ, forestomach and lung tumors were also observed in a high incidence. Carcinogenicity tests on MeIQ are ongoing, and interim data by week 83 show that MeIQ also induces forestomach tumors in addition to liver tumors. In rats, hepatocellular carcinomas were induced by Trp-P-1, Glu-P-1, Glu-P-2, and IQ. In rats given Glu-P-1, Glu-P-2, and IQ, adenocarcinomas in the small and large intestines, squamous cell carcinomas in the Zymbal gland and clitoral gland were also observed in a high incidence.

Animals↗

PubMed1986

Past, present, and future of mutagens in cooked foods.

Mutation assay with Salmonella typhimurium enabled us to detect various types of mutagens in cooked foods. A series of mutagenic heterocyclic amines has been isolated and identified in broiled fish and meat and in pyrolyzates of amino acids and proteins. Feeding experiments showed these mutagens to be carcinogenic in mice and rats. The mechanism of formation and pathway of metabolic activation of these heterocyclic amines have been elucidated. Their contents in various cooked foods have been determined. The presence of mutagenic nitropyrenes (some of which were confirmed as carcinogens) in grilled chicken was also established. Roasted coffee beans also yield mutagens such as methylglyoxal. The formation of mutagen precursors, including beta-carboline derivatives and tyramine which become mutagens with nitrite treatment, was found during food processing. Oncogene activation in animal tumors induced by some of these food mutagens/carcinogens has been confirmed. The role of mutagens/carcinogens in cooked foods in human cancer development has not yet been exactly evaluated. In order to do this, more information on their carcinogenic potency, human intake, metabolism in the human body, and the effects of combined administration with other initiators, promoters and other modifying factors in food is required.

Amino Acids↗

PubMed1986

Mutagens in coffee and other beverages.

A cup of coffee contains mutagens which produce about 5 X 10(4)-10(5) revertants of Salmonella typhimurium TA 100 without S9 mix. One of the mutagens was identified to be methylglyoxal. Methylglyoxal was present in various beverages such as black tea, whisky, and brandy. Methylglyoxal itself induced tumors in rats when administered by subcutaneous injection. However, the mutagenic properties of coffee were different from those of methylglyoxal. The mutagenicity of coffee was suppressed by catalase, and coffee was found to contain hydrogen peroxide. Furthermore, coffee solution was found to have a hydrogen peroxide-generating system. Instant coffee (15 mg/mL) contains 130 microM hydrogen peroxide immediately after the dissolution of coffee powder in water at room temperature. The concentration of hydrogen peroxide increased with time. The mutagenicity of methylglyoxal was increased by the copresence of hydrogen peroxide. A maximum of 30-fold enhancement was observed. The mutagenicity of black tea but not that of whisky was suppressed by catalase.

Animals↗