Let's be scientific about the problem of mutagens in cooked food.
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Biomedical subjects
Publications and source records attributed to T Sugimura.
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The effect of norharman on the metabolism of benzo[alpha]pyrene by rat-liver microsomes was studied. Separation of the metabolites into hydrophilic and hydrophobic fractions showed that norharman inhibited the conversion of hydrophobic metabolites to hydrophilic ones. Analysis of the hydrophobic metabolites by high-pressure liquid chromatography showed that norharman also inhibited the disappearance of benzo[alpha]pyrene itself. However, large amounts of hydrophobic metabolites, such as phenol, quinones and diols, were formed in the presence of norharman, and formation of the strong mutagen 7,8-dihydroxybenzo[alpha]pyrene was increased 10-fold by norharman. The increase in formation of this compound may be one of the chief reasons why norharman enhances the mutagenicity of benzo[alpha]pyrene on Salmonella typhimurium.
The mutagenicity of a spice, sumac, was demonstrated on Salmonella typhimurium strain TA98. The active principle was purified and characterized by thin-layer chromatography, UV-absorption spectroscopy and mass spectrometry. All the mutagenic activity of sumac was found to be due to quercetin.
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Norharman enhanced the known mutagenicity of 2-acetylaminofluorene derivatives in the Salmonella test system. The mutagenicities of 2-acetylaminofluorene, 2-aminofluorene, and N-hydroxy-2-acetylaminofluorene were enhanced by norharman only when rat liver microsomal enzymes were added, whereas the mutagenicity of N-acetoxy-2-acetylaminofluorene was increased in the absence of microsomal enzymes. Harman also increased mutagenesis, althouth less so than norharman.
N-Methyl-N'-nitro-N-nitrosoguanidine (MNNG) was administered orally to male Wistar rats at a concentration of 83 microgram/ml in the drinking water for 2, 4, 5, and 7 months; the rats were killed at about month 15. Intestinal metaplasia was found in the stomachs of 80-100% of the rats treated with MNNG for 4 or more months, of 37.5% treated with MNNG for 2 months, and of 10% of the controls. Metaplastic glands, composed of goblet cells and columnar cells with striated borders, were found in the pyloric region. Paneth's cells were found at the bottom of metaplastic glands in a rat treated with MNNG for 4 months. The incidence of well-differentiated adenocarcinomas of the stomach was 63-90% in rats treated with MNNG for 4 or more months and 25% in those treated with MNNG for 2 months.
Specific antibody against 2'-(5"-phosphoribosyl)-5'AMP (PR-AMP), a monomer of poly(adenosine diphosphate ribose) (poly(ADP-Rib)), was produced by immunizing a rabbit with PR-AMP coupled to bovine serum albumin (BSA). Antibody against PR-AMP was purified 53-fold from serum by (NH4) 2SO4 precipitation, and BSA-Sepharose 4B, DEAE-cellulose and (PR-AMP)-BSA-Sepharose 4B column chromatographies. Inhibition experiments show that the adenine ring, 5'-phosphate residue and ribose-ribose bond of PR-AMP were essential for the antigenic determinant of PR-AMP. Anti PR-AMP antibody bound, not only with PR-AMP, but also with poly(ADP-Rib) of various chain lengths, while anti poly(ADP-Rib) antibody bound with poly(ADP-Rib) but not with PR-AMP.
An electrophoretic system was established that resolves poly(adenosine diphosphate ribose), enzymatically synthesized polymer from NAD+, by size difference of one residue on polyacrylamide gel. The existence of a polymer of at least 65 residues was demonstrated by band counting in this system. The polymer showed a heterogeneous size distribution on the electrophoregram, and the molecular weight of the largest polymer was deduced to be more than 4.5 X 10(5) daltons. The discrepancy between the size, estimated by electrophoresis, and the chain length, determined by the ratio of total radioactivity to that derived from the terminus, suggests that the polymer has a branched structure.
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Electron microphotographs showed that pancreatic acinar cells contain many dense zymogen granules in the fetal stage (day 21 of gestation), both dense and less dense granules in the infant stage (day 10 after birth) and again only dense granules in the adult stage. Injection of dexamethasone in the infant stage greatly increased the number of dense granules, and slightly increased the total number of granules, whereas its injection in the weanling stage (day 24 after birth) did not increase the total number of zymogen granules or their density. Parotid acinar cells contain many zymogen granules of low density in the weanling stage (day 24 after birth), and granules of low density with dense spots in the adult stage. Injection of dexamethasone in the weanling stage increased the number of adult-type zymogen granules, but did not increase the total number of granules. The developmental change in amylase activity was parallel with the change in the high-density areas in zymogen granules, and the latter seemed to be influenced by the serum glucocorticoid level.
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Carcinogenicity of seven homologs of N-alkyl-N'-nitrosoguanidine (N-alkyl-NNG), namely, N-methyl-NNG, N-propyl-NNG, N-butyl-NNG, N-isobutyl-NNG, N-pentyl-NNG, and N-hexyl-NNG, was examined by injecting the compounds subcutaneously into rats. All of them except N-isobutyl-NNG and N-hexyl-NNG were carcinogenic, but N-ethyl-NNG followed by N-methyl-NNG were stronger carcinogens than those with longer alkyl chains.
The polyethylene glycol (PEG) precipitation method was used for the concentration and purification of eight bovine viruses. Good results were obtained from four viruses, parainfluenza--3 virus, bovine enterovirus, bovine adenovirus, and bovine parvovirus. No satisfactory results of concentration were obtained from bovine reovirus, bovine viral diarrhea virus, and infectious bovine rhinotracheitis virus. The failure of concentration of the four viruses seems to be ascribed rather to the resuspending of virus from the virus--PEG precipitate than to the precipitation of virus from infective culture fluid. This method can be applied as the initial step to the concentration of parainfluenza--3 virus, bovine enterovirus, bovine adenovirus, and bovine parvovirus from a large volume of material, since it is simple, rapid, and inexpensive.
The differentiated functions of phagocytosis, locomotion, and morphological changes into cells resembling granulocytes and macrophages were induced in cultured mouse myeloid leukemic cells, M1 clone 34, by treatment with human saliva. The rates of induction of these differentiated phenotypes were proportional to the concentration of saliva added and the period of treatment. The factor inducing differentiation was nondialyzable and heat labile. This factor was purified 70-fold by fractionation with Diaflo membranes and DE52 column chromatography. The activities inducing the three differentiated characters examined were purified together, suggesting that they were all due to the same factor.
An antitumor antibiotic aclacinomycin A, was nonmutagenic in a Salmonella test, but its derivative, N-demethylaclacinomycin A, was mutagenic. Similarly, 1-deoxypyrromycin, a hydrolysis product of aclacinomycin A, was nonmutagenic, but N-demethyl-1-deoxypyrromycin was mutagenic. Daunomycin was highly mutagenic, but N-methyldaunomycin showed only weak mutagenicity, and N-dimethyldaunomycin was nonmutagenic. The aglycones of aclacinomycin A and daunomycin were not mutagenic. Thus, the amino moiety of anthracycline glycosides is concluded to be essential for mutagenesis.