Mutagens and carcinogens in cooked food.
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Amines↗
Biomedical subjects
T Sugimura
Publications and source records attributed to T Sugimura.
Histologic demonstration of antigens reactive with anti-p21 ras monoclonal antibody (RAP-5) in human stomach cancers.
The immunohistochemical reactivity of RAP-5, a monoclonal antibody (MoAb) raised against a synthetic peptide corresponding to positions 10-17 of the ras gene product from T24 bladder carcinoma, was studied in 96 surgically resected stomach cancers of humans. The cytoplasm of cancer cells in 65 cases (68%) was positively stained with MoAb RAP-5, although the staining was heterogeneous among cancer cells. There was no definite correlation between depth of tumor invasion and reactivity to MoAb RAP-5. Cancer cells of poorly differentiated tumors showed a tendency to react less frequently and less intensely to MoAb RAP-5. In nontumorous gastric mucosa, parietal cells and some portions of intestinal metaplasia were stained with MoAb RAP-5. These findings suggest an increased expression of the ras gene product (p21) in about two-thirds of gastric adenocarcinomas and in some nonneoplastic gastric epithelial cells.
Antibodies, Monoclonal↗
What is the role of environmental mutagens for human cancer development?
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Amines↗
Methylglyoxal in beverages and foods: its mutagenicity and carcinogenicity.
Methylglyoxal was found to induce mutations in Salmonella typhimurium strains TA100, TA102 and TA104, gene conversion in Saccharomyces cerevisiae strain D7, and diphtheria toxin resistance mutation in Chinese hamster lung cells. Methylglyoxal was detected in coffee, whiskey, a soft drink, toasted bread and soy sauce. The mutagenicity of methylglyoxal was suppressed by sulfite, cysteine, glutathione and dithiothreitol, and enhanced by hydrogen peroxide. Methylglyoxal induced sarcomas in rats at the site of its subcutaneous injection.
Aldehydes↗
Carcinogenicity of dinitropyrenes in rats and hamsters.
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Animals↗
Sequential changes of mouse bladder epithelium during induction of invasive carcinomas by N-butyl-N-(4-hydroxybutyl)nitrosamine.
Invasive carcinoma of the bladder in humans shows aggressive growth with poor prognosis. Little is known about its preceding lesions. Sequential changes of the bladder epithelium following administration of N-butyl-N-(4-hydroxybutyl)nitrosamine (BHBN) were studied in mice. Female C3H/He mice were divided into 4 groups. Three groups were given 0.05, 0.01, and 0.005% concentrations of BHBN, respectively, in their drinking water, and the control group was given tap water. The mice were killed at regular intervals over a period of 26 weeks, and their bladder epithelium was examined histologically. Dysplasia, carcinoma in situ, and invasive carcinoma were observed sequentially in the groups treated with BHBN, and the incidences of dysplasia, carcinoma in situ, and invasive carcinoma were dependent on the dose of BHBN. The data indicate that bladder carcinoma in mice is a good model of invasive bladder carcinoma in humans, although it is not fully compatible with the human model because of the complete absence of metastases.
Animals↗
Detection of mutant diphtheria toxin-resistant Chinese hamster lung cells in situ by autoradiography.
An autoradiographic method was developed to detect diphtheria toxin-resistant (DTr) Chinese hamster lung cells in situ. With this method, a dose-dependent increase in the number of DTr cells was observed after exposure of the cells to increasing concentrations of ethyl methanesulfonate (EMS). Segregation of EMS-induced DTr cells in a sector of single colonies was clearly demonstrated. It was also found by this method that the number of DTr cells induced by a fixed concentration of EMS was not determined by the number of cell divisions during the expression time but by the period after exposure of the cells to EMS.
Animals↗
Mutagenic compounds in soy sauce, Chinese cabbage, coffee and herbal teas.
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Brassica↗
Activated c-raf gene in a rat hepatocellular carcinoma induced by 2-amino-3-methylimidazo[4,5-f]quinoline.
A rat hepatocellular carcinoma, IQ7, induced by 2-amino-3-methylimidazo[4,5-f]quinoline (IQ) gave two transformants of NIH 3T3 cells on DNA mediated gene transfer. One of these transformants was examined further and secondary and tertiary transformants were obtained. The secondary transformant was tumorigenic in nude mice. The activated oncogene in this primary transformant was identified as rat c-raf by Southern blot analysis.
Animals↗
Amplified DNA sequences in cancers.
Amplification of genes other than known oncogenes was analyzed using an in-gel DNA renaturation method, in which a mixture of restriction fragments of radioactively labelled tracer DNA and unlabelled driver DNA was electrophoresed and amplified DNA fragments were visualized after two cycles of denaturation and renaturation in the gel. Different DNA fragments were found to be amplified more than 400 fold in NB1, a neuroblastoma cell line, in Y79, a retinoblastoma cell line and in H69, a small cell lung carcinoma cell line, in addition to 120 to 160-fold amplification of N-myc gene in these three cell lines.
Cell Line↗
Methylation pattern of human T-cell leukemia virus in vivo and in vitro: pX and LTR regions are hypomethylated in vivo.
The methylation patterns of the gag, pol, env, pX and LTR regions of proviral DNA of human T-cell leukemia/lymphoma virus type I (HTLV) in fresh leukemic cells and established cell lines were examined using HpaII/MspI endonuclease. Peripheral blood lymphocytes (PBL) isolated from patients with adult T-cell leukemia/lymphoma (ATL) did not express viral antigens of HTLV, but PBL that had been cultured for 2 days did express these viral antigens. Most parts of the gag, pol and env regions of the HTLV provirus in PBL isolated from 12 ATL patients and PBL cultured for 2 days were hypermethylated as reported by others. In contrast, in 10 established cell lines that harbored HTLV genomes and expressed viral antigens, HTLV proviruses were hypomethylated. In one cell line, ATL-IK, which harbored an HTLV genome but did not produce viral antigens, the gag, pol and env regions were hypermethylated. However, two HpaII sites, one in the middle of the gag region and the other in the middle of the pol region, were not methylated even in PBL from most ATL patients. Furthermore, the pX and LTR regions were hypomethylated not only in established cell lines but also in PBL of ATL patients. The hypomethylation of the pX and LTR regions detected in fresh leukemic cells of ATL patients may have some etiological significance in cell transformation by controlling the level of transcription of these regions, or modulating the binding of some factors to these regions.
Adult↗
Stimulation of prostaglandin E2 production by 12-O-tetradecanoylphorbol 13-acetate (TPA)-type and non-TPA-type tumor promoters in macrophages and its inhibition by cycloheximide.
The effects of TPA (12-O-tetradecanoylphorbol 13-acetate)-type and non-TPA-type tumor promoters on prostaglandin E2 production by peritoneal macrophages of rats were examined. Among the TPA-type tumor promoters, aplysiatoxin was most potent in stimulating prostaglandin E2 production followed by dihydroteleocidin B, teleocidin, TPA and debromoaplysiatoxin. Prostaglandin E2 production by aplysiatoxin treatment was stimulated at doses up to 0.1 ng/ml. Palytoxin, a non-TPA-type tumor promoter, also stimulated both prostaglandin E2 production and the release of radioactivity from [3H]arachidonic acid-labeled macrophages. However, the dose required for the expression of these effects by palytoxin was up to 3 pg/ml. It was suggested that the tumor promoters are associated with the activity to stimulate arachidonic acid metabolism, irrespective of their type. Cycloheximide, a protein synthesis inhibitor, inhibited both prostaglandin E2 production and the release of radioactivity from prelabeled macrophages stimulated either by the TPA-type tumor promoters or by the non-TPA-type tumor promoter. It is possible that the tumor promoters may induce the synthesis of some proteins responsible for the stimulation of arachidonate metabolism.
Acrylamides↗
Appearance of albumin-producing cells in the liver of analbuminemic rats on aging and administration of mutagens.
The lack in serum albumin in analbuminemic rats, a strain derived from Sprague-Dawley rats, was found to be due to deficient synthesis of albumin in the liver caused by a disturbance in the processing of albumin mRNA. The serum albumin gene was cloned from analbuminemic rats and from parental normal Sprague-Dawley rats. Analyses of the nucleotide sequences of these albumin genes revealed that there is a seven base pair deletion in the HI intron of the albumin gene of analbuminemic rats. This deletion extends from the 5th to the 11th base of the 5'-end of the intron causing change in the nucleotide sequence of the 5'-end of the HI intron from GTAGGTT to GTAGCGA. The HI intron sequence was found to be accumulated in the nuclear RNA of analbuminemic rat liver indicating blocking of mRNA splicing. Although analbuminemic rats are almost completely deficient in serum albumin, a small but appreciable amount of "albumin" was detected in their serum. This protein was purified by immunoprecipitation and SDS-gel electrophoresis and shown to have the same immunological crossreactivity and digestion patterns with V8 protease and papain as those of normal rat serum albumin. The concentration of "albumin" increased slightly upon aging of analbuminemic rats. The existence of serum albumin in hepatocytes of analbuminemic rats was studied immunohistochemically by the peroxidase anti-peroxidase method. There were about 1/10(5) albumin-positive cells, presumably albumin-producing hepatocytes at birth, and their number increased gradually to 100 approximately 200/10(4) about 24 months after birth. When the hepatocarcionogenic mutagen 3'-methyl-4-dimethylaminoazobenzene was administered to analbuminemic rats, the number of albumin-positive cells in the liver increased 8-fold in 5 weeks and 10-fold in 15 weeks. A similar increase was observed after administration of acetylaminofluorene, but not after partial hepatectomy or administration of diethylnitrosamine.
Aging↗
Use of nitrite and hypochlorite treatments in determination of the contributions of IQ-type and non-IQ-type heterocyclic amines to the mutagenicities in crude pyrolyzed materials.
The mutagenic heterocyclic amines Glu-P-2, MeA alpha C and Phe-P-1, which possess a 2-aminopyridine structure in their molecule (non-IQ-type mutagens), were found to be inactivated by nitrite treatment under acidic conditions, as observed previously with Trp-P-1, Trp-P-2, Glu-P-1 and A alpha C. In contrast, MeIQx, 4,8- and 7,8-DiMeIQx, which were originally isolated from fried beef or heated model mixtures of creatinine, amino acids and glucose, and which have a 2-aminoimidazole moiety in their molecules (IQ-type mutagens), were very resistant to nitrite treatment like IQ and MeIQ. Both types of mutagenic heterocyclic amines were completely inactivated by treatment with hypochlorite. This differential inactivation of mutagenic heterocyclic amines by nitrite and hypochlorite was used in determination of the contributions of IQ-type and non-IQ-type mutagens to the total mutagenicities of various pyrolyzed materials. The percentage contributions of IQ-type mutagens to the mutagenicities of broiled sardine, fried beef, broiled horse mackerel, cigarette smoke condensate and albumin tar were 88, 75, 48, 6 and 4, respectively.
Amines↗
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↗
Characteristics of major mutagenicity of instant coffee.
Detailed quantitative studies on the mutagenicity of methylglyoxal showed that its contribution to the total mutagenicity of instant coffee on S. typhimurium TA100 was minor although we reported previously (Kasai et al., 1982) that its contribution to the mutagenicity of freshly brewed coffee was about 50%. Cysteine suppressed the mutagenicity of methylglyoxal and of methylglyoxal when added to instant coffee, but did not affect the mutagenicity of coffee itself. Catalase suppressed most of the mutagenicity of coffee, but not that of methylglyoxal or of methylglyoxal added to coffee.
Catalase↗
Implication of hydrogen peroxide in the mutagenicity of coffee.
A cup of instant coffee (150 ml) of normal strength (15 mg/ml) was found to contain about 500 and 750 micrograms of hydrogen peroxide soon after its preparation at 37 degrees C and 80 degrees C, respectively, but the concentration of hydrogen peroxide in the coffee increased with time for up to 24 h after its preparation. Thus coffee contains a hydrogen peroxide generating system. As extracts of green coffee beans were found to have very low capacity to generate hydrogen peroxide, this generating system is produced by roasting coffee beans. Hydrogen peroxide itself was only weakly mutagenic to Salmonella typhimurium TA100, but in the presence of methylglyoxal, which is also present as a mutagenic component in coffee, hydrogen peroxide showed strong mutagenicity. Hydrogen peroxide and methylglyoxal seem to be responsible for most of the mutagenicity of instant coffee.
Aldehydes↗
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↗