PubMed Health⌕ Search

Biomedical subjects

T Yahagi

Publications and source records attributed to T Yahagi.

At least 37 records · Page 2Linked to original sources

Pyrolysis products from amino acids and protein: highest mutagenicity requires cytochrome P1-450.

Pyrolysis products of proteins and amino acids are highly mutagenic, but metabolism of these chemicals by rat liver subcellular fractions is known to be required for production of the mutagenic intermediates. We examined the mutagenesis of seven purified pyrolysis products from tryptophan, lysine, glutamic acid, and soybean globulin with Salmonella typhimurium strain TA98 in the presence of liver fractions from genetically "responsive" C57BL/6N and Ah(b)/Ah(d) or "nonresponsive" DBA/2N and Ah(d)/Ah(d) mice that had been pretreated in vivo with benzo[a]pyrene. For all pyrolysis products tested, mutagenesis is 2-fold to more than 1000-fold greater with C57BL/6N and Ah(b)/Ah(d) than with DBA/2N or Ah(d)/Ah(d) liver fractions. A sucrose density gradient assay for detecting the Ah regulatory gene product, the receptor, was studied with C57BL/6N hepatic cytosol. At levels 100 times in excess of [1,6-(3)H]2,3,7,8-tetrachlorodibenzo-p-dioxin, nonlabeled 2,3,7,8-tetrachlorodibenzo-p-dioxin, 3-methylcholanthrene, and beta-naphthoflavone (inducers of cytochrome P(1)-450) are able to displace the radioligand from its hepatic cytosolic receptor; four pyrolysates from tryptophan, glutamic acid, and soybean globulin did not have this capacity. These data indicate that the pyrolysis products tested, although not effective as inducers of cytochrome P(1)-450, are most mutagenic when metabolized by P(1)-450. Potent P(1)-450 inducers-present in pyrolysates during the combustion process-might be present in quantities insufficient to initiate mutagenesis or carcinogenesis but might have a synergistic action, or act as "comutagens" or "cocarcinogens," with the N-containing heterocyclic pyrolysis products. A quantitative relationship between mutagenic and carcinogenic potency of these pyrolysis products remains, however, to be demonstrated.

Amino Acids↗

The effect of norharman on the metabolism of benzo[alpha]pyrene by rat-liver microsomes in vitro in relation to its enhancement of the mutagenicity of benzo[alpha]pyrene.

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.

Alkaloids↗

Identification of a mutagenic substance in a spice, sumac, as quercetin.

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.

Chromatography, Thin Layer↗

Mutagenicity of several classes of antitumor agents to Salmonella typhimurium TA98, TA100, and TA92.

The mutagenic activities of antitumor agents, including 5 antibiotics, 19 antimetabolites, 5 alkylating agents, 2 alkaloids, 1 enzyme, and 1 adrenal steroid hormone, were tested on Salmonella tyhimurium TA100, TA98, and TA92. Four of these, busulfan, carbazilquinone, 1-(4-amino-2-methylpyrimidine-5-yl)methyl-3-(2-chloroethyl)-3-nitrosourea hydrochloride, and pipobroman were shown for the first time to be mutagenic. Further, the known mutagenicities of five others, daunomycin hydrochloride, Adriamycin hydrochloride, mitomycin C, 6-mercaptopurine, and cyclophosphamide, were confirmed.

Alkylating Agents↗

Mutagenicities of N-nitrosamines on Salmonella.

The mutagenic activities of 11 N-nitrosamines were tested using Salmonella typhimurium TA100 and TA98. All the carcinogenic N-nitrosamines were mutagenic on TA100 with a drug-activating system from the rat liver, whereas N,N-diphenylnitrosamine, a non-carcinogen, was not mutagenic. None of the N-nitrosamines was mutagenic on TA98, except N,N-diethylnitrosamine which was weakly mutagenic. To detect the mutagenicity of N,N-dimethylnitrosamine, the pre-incubation of bacteria and N,N-dimethylnitrosamine with S-9 Mix before if was poured onto plates was obligatorily required. Dimethyl sulfoxide inhibited the mutagenic effect of N,N-dimethylnitrosamine.

Animals↗

Mutagenicities of quinoline and its derivatives.

Quinoline, recently reported to be carcinogenic in rats [12], was mutagenic to Salmonella typhimurium tester strains TA100 and TA98 in the presence of the metabolic activation system S-9 mix. 2-Chloroquinoline, a non-carcinogen [12], was non-mutagenic with or without S-9 mix. 8-Hydroxyquinoline, which is t known to be carcinogenic, was mutagenic with S-9 mix to both bacterial strains. The mutagenicities of 17 other quinoline derivatives that are not known to be carcinogenic were tested, and 12 of these compounds were mutagenic.

Animals↗

Mutagenicities of protein pyrolysates.

Smoke condensate obtained by pyrolysis of proteins, such as lysozyme and histone, was shown to be mutagenic to Salmonella typhimurium TA100 and TA98. In vitro metabolic activation by a mammaliam postmitochondrial enzyme preparation (S-9 Mix) was required. Smoke condensates obtained by pyrolysis of DNA, RNA, starch and vegetable oil were slightly mutagenic, whereas those from pyrolysis of L- and D-tryptophan and 5-hydroxy-D,L-tryptophan were very strongly mutagenic with metabolic activation by S-9 Mix. Because of the high correlation between mutagenicity and carcinogenicity, it is theorized that the cooking of proteinaceous foods might be an important cause of human cancers.

5-Hydroxytryptophan↗

Mutagenicities of smoke condensates and the charred surface of fish and meat.

Smoke condensates obtained from broiling fish showed mutagenic activity for Salmonella typhimurium TA100 and TA98. Metabolic activation was required to induce mutagenic activity of smoke condensates of some species of fish. The smoke condensate obtained during charcoal broiling of beefsteak was far less mutagenic than that of fish, with or without metabolic activation. Extracts of the charred surface of broiled fish and meat also contained mutagenic substances. These extracts needed metabolic activation to exhibit mutagenicities on TA98. The mutagenic activity of the smoke condensate obtained from one sardine weighing 100 g was equivalent to that of 132 micrograms benzo(a)pyrene and that of the charred surface of the sardine was equivalent to 358 micrograms benzo(a)pyrene. One piece of beefsteak weighing 190 g, contained mutagenic activity equivalent to that of 855 micrograns benzo(a)pyrene.

Animals↗

Mutagenicity of smoke condensates from cigarettes, cigars and pipe tobacco.

Smoke condensates from cigarettes, cigars and pipe tobacco were mutagenic on Salmonella typhimurium TA100 and TA98 when activated with rat liver microsomal system. Mutagenicity of a unit weight of smoke condensate was rather high in cigars, low in pipe tobacco and intermediate in cigarettes. Specific mutagenic activity was almost comparable among smoke condensates from low- to high-tar cigarettes, although some variations were observed depending upon the country producing the cigarettes. Marked mutagenicity of cigarette smoke condensate could not be explained by the benzo (a) pyrene or nitroso compounds it actually contained, suggesting the presence of other very potent mutagens in tobacco smoke condensates.

Animals↗

Mutagenicity of N-butyl-N-(4-hydroxybutyl)nitrosamine, a bladder carcinogen, and related compounds.

N-Butyl-N-(4-hydroxybutyl)nitrosamine (BBN), which specifically induces bladder tumors, was shown to be mutagenic to Salmonella typhimurium strains TA 1535 and TA100 in the presence of an S-9 mix prepared from the liver of rats treated with polychlorinated biphenyl. Reduced nicotinamide adenine dinucleotide was a more effective cofactor than reduced nicotinamide adenine dinucleotide phosphate in the activation of BBN by the rat liver S-9 fraction, N-Butyl-N-(3-carboxypropyl)nitrosamine, reported to be the main urinary metabolite of BBN as well as of N,N-dibutylnitrosamine and to induce urinary bladder tumors specifically, was found to be mutagenic without metabolic activation by the S-9 mix. The mutagenicities of 31 compounds related structurally or metabolically to BBN and N,N-dibutylnitrosamine were tested. Of these compounds, 13 have previously been demonstrated to be carcinogenic, and nine have been shown to be noncarcinogenic. All the carcinogenic compounds were found to be mutagenic to strain TA1535 with or without the S-9 mix. Four of the nine noncarcinogenic compounds were also mutagenic. These "false-positive" compounds were predicted, in fact, to be carcinogenic.

Animals↗

Mutagenicities of nitrofuran derivatives on a bacterial tester strain with an R factor plasmid.

Many nitrofuran derivatives are known to be mutagenic on Escherichia coli WP2 but not on Salmonella typhimurium TA1535, TA1536, TA1537 or TA1538. Ames and coworkers recently obtained a new tester strain of S. typhimurium, TA100, by putting an R factor plasmid, pKM101, into TA1535. We found that all mutagenic nitrofuran derivatives previously found to be mutagenic on E. coli WP2 were mutagenic on this new strain (TA100).

Drug Resistance, Microbial↗

Mutagenicity of carcinogenic azo dyes and their derivatives.

The mutagenicity of N,N-dimethyl-4-aminoazobenzene and N-methyl-4-aminoazobenzene and their derivatives was shown on Salmonella typhimurium TA100 and TA98. S-9 Mix, obtained from rat liver after injection of polychlorinated biphenyl, was abligatory for their mutagenic action. N-Acetoxy-N-methyl-4-aminoazobenzene and N-benzoyloxy-N-methyl-4-aminoazobenzene and their 4'-methoxycarbonyl derivatives were also mutagenic on TA100 and TA98 and did not require metabolic activation by S-9 Mix. It is suggested that the carcinogenic effects of azo dyes may involve modification of DNA.

Animals↗

Mutagenicity of 5-nitroacenaphthene in salmonella.

5-Nitroacenaphthene was proved to be mutagenic on TA100 and TA98 of Salmonella typhimurium with or without metabolic activation by S-9 Mix. A possible metabolite, 5-hydroxyacenaphthene, carcinogenicity of which had not been observed, was non-mutagenic on TA100 and TA98, with or without metabolic activation.

Acenaphthenes↗